Journal of Clinical Laboratory Analysis

The establishment of a multiplex fluorescent polymerase chain reaction coupled with capillary electrophoresis analysis technology enables the simultaneous detection of 16 genotypes of human papillomavirus

AbstractBackgroundThe detection and accurate genotyping of human papillomavirus (HPV) infection is critical for preventing and effectively treating cervical cancer.MethodsA multiplex fluorescent polymerase chain reaction (PCR) coupled with a capillary electrophoresis method was developed for the simultaneous detection of the 16 most prevalent HPV genotypes. Twenty‐five pairs of primers were ultimately selected to ensure that both E and L regions of nine HPV genotypes, as well as the E regions of seven HPV genotypes could be accurately amplified.ResultsThis method enables the simultaneous detection and differentiation of 16 HPV genotypes in a single closed‐tube reaction, accurately distinguishing products with molecular weight differences >1 bp through capillary electrophoresis. This method demonstrated exceptional accuracy, specificity, and repeatability with a detection limit of 10 copies/μL for all 16 HPV genotypes. Furthermore, 152 cervical swab specimens were obtained to compare the disparities between this approach and Cobas 4800 HPV detection method. The concordance rate and κ value were 90.1% and 0.802, respectively, indicating a high level of agreement. The established detection method was successfully applied to cervical swab specimens for determining HPV genotypes across all levels of cervical lesions, HPV52, 56, 16, and 59 were found to be most prevalent with infection rates of 10.8%, 9.1%, 6.5%, and 6.2%, respectively.ConclusionsThis study has successfully established a detection method capable of simultaneously identifying 16 HPV genotypes. This approach can be further applied to HPV vaccine research and surveillance, with the potential for broad applications.

DNA‐Based Liquid Biopsy for Evaluating Surgical and Postsurgical Outcomes in Gynecologic Malignancies: A Systematic Review

ABSTRACT Introduction DNA‐based liquid biopsies, including circulating tumor DNA (ctDNA) and cell‐free DNA (cfDNA), are emerging as minimally invasive biomarkers for monitoring surgical and postsurgical outcomes in gynecologic malignancies. These tools offer the potential to guide early intervention, refine risk stratification, and improve prognostic accuracy. This systematic review aimed to assess the clinical utility of DNA‐based liquid biopsies in evaluating recurrence, surgical success, and preoperative diagnosis in gynecologic cancers. Methods A systematic review was conducted in accordance with PRISMA guidelines, covering studies published from 2017 to 2025. Literature searches were performed in PubMed, Scopus, and Web of Science. A total of 32 eligible observational studies involving 3210 patients with ovarian, endometrial, uterine, and other gynecologic malignancies were included. Study quality was assessed using the Newcastle‐Ottawa Scale (NOS). Results The studies showed a broad geographic and methodological diversity, with a median NOS score of 7. CtDNA and cfDNA demonstrated promise in three key areas: (1) Recurrence prediction—postoperative ctDNA positivity was associated with higher relapse rates and reduced disease‐free survival; (2) Monitoring surgical outcomes and treatment response—ctDNA dynamics more accurately reflected tumor burden than traditional markers like CA125; (3) Preoperative diagnostic support—cfDNA methylation profiling and cfDNA/CA125 models enhanced malignancy detection and risk stratification. Ovarian and endometrial cancers were most frequently studied. Conclusions DNA‐based liquid biopsies show strong potential in perioperative care for gynecologic cancers. Their integration into clinical workflows could improve the detection of minimal residual disease and inform individualized surgical planning.

Performance Evaluation of a New HRD Assay (HRDsig) in Ovarian Carcinomas in Australia

ABSTRACTBackgroundHomologous recombination repair (HRR) is the preferred pathway for repairing double‐strand DNA breaks, using proteins like BRCA1 and BRCA2, among others, while the PARP‐mediated repair pathway is primarily used for single‐strand breaks. When a tumour becomes HRR‐deficient (HRD), then those tumour cells become reliant on PARP‐mediated repair. Poly ADP‐ribose polymerase inhibitors, olaparib and niraparib, have been approved in Australia for advanced (FIGO III‐IV), high‐grade serous or other high‐grade ovarian, fallopian tube or primary peritoneal carcinoma with homologous recombination deficiency (HRD).MethodsHRDsig (Roche Inc) is a new HRD biomarker that is part of the AVENIO Tumor Tissue CGP Kit V2. We have studied the performance of HRDsig against two NATA (National Association of Testing Authorities, Australia) accredited HRD assays in the cases of high‐grade ovarian carcinomas. We have evaluated the performance of HRDsig using a total 40 HRD results against the two accredited HRD assays, as well as against commercial controls and inter‐laboratory comparison samples.ResultsHRDsig has demonstrated a high concordance rate for HRD by comparing it with two different locally accredited HRD assays in cases of ovarian cancers.ConclusionThese findings provide real‐world evidence of the performance of a new HRD assay (HRDsig) in ovarian carcinomas.

m6A‐related long noncoding RNAs predict prognosis and indicate therapeutic response in endometrial carcinoma

AbstractBackgroundN6‐methyladenosine (m6A) has been identified as the most common, abundant, and conserved internal transcriptional modification. Long noncoding RNAs (lncRNAs) are noncoding RNAs consisting of more than 200 nucleotides, and the expression of various lncRNAs may affect cancer prognosis. The impact of m6A‐associated lncRNAs on uterine corpus endometrial carcinoma (UCEC) prognosis is unknown.MethodsIn this study, UCEC prognosis‐related m6A lncRNAs were screened, bioinformatics analysis was performed, and experimental validation was conducted. Endometrial carcinoma (EC) and normal tissue samples were obtained from The Cancer Genome Atlas. The prognosis‐related m6A lncRNAs screened by the least absolute shrinkage and selection operator method were used for multivariate Cox proportional risk regression modeling. Principal component analysis and Gene Ontology, immune function difference, and drug sensitivity analyses of the prognostic models were performed. Prognostic analysis was conducted for m6A‐associated lncRNAs. The immune infiltration relationship of m6A‐associated lncRNAs in EC was identified using the ssGSEA immune infiltration algorithm. A competing endogenouse RNA network was constructed using the LncACTdb database. Finally, quantitative real‐time polymerase chain reaction (qRT‐PCR) assays were used to validate the differences in m6A‐related lncRNA expression in normal and EC cells.ResultsCDKN2B‐AS1 and MIR924HG were found to be risk factors for EC. RAB11B‐AS1 was a protective factor in EC patients. MIR924HG expression was upregulated in KLE and RL95‐2 endometrial cancer cell lines. Prognostic models involved RAB11B‐AS1, LINC01812, HM13‐IT1, TPM1‐AS, SLC16A1‐AS1, LINC01936, and CDKN2B‐AS1. The high‐risk group was more sensitive to five compounds (ABT.263, ABT.888, AP.24534, ATRA, and AZD.0530) than the low‐risk group.ConclusionThese findings contribute to understanding of the function of m6A‐related lncRNAs in UCEC and provide promising therapeutic strategies for UCEC.

GLP1R inhibits the progression of endometrial carcinoma through activation of cAMP / PKA pathway

Abstract Background This study strived to explore the role and mechanism of glucagon‐like peptide‐1 receptor (GLP1R) in endometrial carcinoma (EC). Methods In detail, after transfection of GLP1R overexpression vector and small interfering RNA targeting PKA, the mRNA expressions of GLP1R and PKA in EC cells (Ishikawa and RL95‐2) were quantified by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The cell biological behaviors, including proliferation, migration, invasion, and apoptosis, were detected using 5‐ethynyl‐2′‐deoxyuridine (EdU), wound healing, transwell, and flow cytometry assays, respectively. The cyclic adenosine monophosphate (cAMP) content and related protein expressions (GLP1R, p‐PKA, and PKA) were determined by enzyme‐linked immunosorbent assay (ELISA) and western blot. The effects of GLP1R and PKA on tumorigenesis were evaluated by measuring the tumor volume and weight of mice bearing EC. Result According to the results, GLP1R expression was downregulated in EC tissues and cells, and there was a positive correlation between GLP1R and PKA expressions. Upregulation of GLP1R promoted apoptosis and activated the cAMP/PKA signaling pathway in EC cells, while hindering the EC cell proliferation, invasion, migration, and the growth of tumor in mice. However, these effects were blunted by downregulation of PKA, which also accelerated the progression of EC in vitro and in vivo via inhibiting the activation of cAMP/PKA signaling pathway. Conclusion Collectively, upregulation of GLP1R impeded EC progression via inducing the activation of cAMP/PKA signaling pathway, which may be a potential treatment for EC.

Aberrant TRPC1 expression reflects stromal cervical invasion, lymphovascular invasion, elevated FIGO stage, and poor survival in resectable endometrial carcinoma patients

AbstractBackgroundTransient receptor potential channel 1 (TRPC1) promotes tumor growth and metastasis in endometrial carcinoma (EC) cell lines, whereas its clinical role in EC management remains unclear. Therefore, this study aimed to investigate the association of TRPC1 protein expression with the clinical features and survival of EC patients, then was further validated by TRPC1 mRNA measurement and data from The Human Protein Atlas.MethodsTRPC1 protein expression in tumor tissues and normal endometria of 176 resectable EC patients was determined using immunohistochemistry. Besides, TRPC1 mRNA expression of partial patients (n = 80) was detected using RT‐qPCR. Additionally, survival data from The Human Protein Atlas (derived from The Cancer Genome Atlas [TCGA]) was analyzed.ResultsTRPC1 protein expression was up‐regulated in tumor tissue compared with normal endometrium (p < 0.001). Up‐regulated TRPC1 protein expression was associated with stromal cervical invasion (p = 0.044), lymphovascular invasion (p = 0.032), and increased federation of gynecology and obstetrics (FIGO) stage (p = 0.005). Tumor TRPC1 protein high was linked with shortened accumulating disease‐free survival (DFS) (p = 0.009) and overall survival (OS) (p = 0.026), which were also confirmed by multivariate Cox's regression analysis (both p < 0.050). Further, TRPC1 mRNA validation disclosed that TRPC1 mRNA high was related to shortened accumulating DFS (p = 0.038) and exhibited a correlating trend with declined OS (lacked statistical significance) (p = 0.162). Meanwhile, survival analysis on the data from The Human Protein Atlas (derived from TCGA) also exhibited that TRPC1 mRNA high was correlated with reduced accumulating OS (p < 0.001).ConclusionOur findings support TRPC1 as a prognostic biomarker in resectable EC patients.

Blocking PARP activity with the inhibitor veliparib enhances radiotherapy sensitivity in endometrial carcinoma

AbstractObjectiveOur study aimed to investigate the potential clinical utility of a poly(ADP‐ribose) polymerase (PARP) inhibitor, veliparib (ABT‐888), as a radiosensitizer in the medication of endometrial carcinoma (EC).MethodsHuman Ishikawa endometrial adenocarcinoma cells were treated with veliparib, radiotherapy (RT), or combination treatment. The viabilities, radiosensitivity enhancement ratio (sensitizer enhancement ratio (SER), and apoptosis of Ishikawa cells were, respectively, evaluated by Cell Counting Kit‐8 (CCK‐8), colony formation experiment, and flow cytometry. The tumor growth was assessed by xenograft mice models. Western blot assay investigated the expression of DNA damage and apoptosis‐related proteins in vivo and in vitro.ResultsCell Counting Kit‐8 revealed that the 10% inhibition concentration (IC10) and 50% inhibition concentration (IC50) values of veliparib‐treated Ishikawa cells were 1.7 and 133.5 µM, respectively. The SER of veliparib combined with RT was 1.229 in vitro. Flow cytometry analysis results indicated that the apoptosis rate of the veliparib + RT group was markedly higher than that of the RT group in vitro (p < 0.05). Furthermore, in vivo data revealed that veliparib + RT treatment significantly decreased tumor growth compared with single treatments of veliparib or RT and with the control group (p < 0.05). Then western blot confirmed the levels of anti‐phospho‐histone (γH2AX), caspase‐3, and B‐cell lymphoma 2 (Bcl‐2) associated protein X (Bax) were significantly higher in the veliparib + RT group, while the level of Bcl‐2 was lower compared with that of the RT group (p < 0.05), both in vivo and in vitro.ConclusionOur results indicate that veliparib in combination with RT markedly improved the therapeutic efficiency in human endometrial carcinoma.

High expression of the ferroptosis‐associated MGST1 gene in relation to poor outcome and maladjusted immune cell infiltration in uterine corpus endometrial carcinoma

AbstractBackgroundUterine corpus endometrial carcinoma (UCEC) tightly correlates with dysregulated iron homeostasis. MGST1 (microsomal glutathione S‐transferase 1) involves in the regulation of oxidative stress and plays a key role in inhibiting iron‐mediated cell death in cancer cells. Hence, we aimed to illuminate the characteristics of MGST1 expression and prognosis in UCEC using bioinformatics prediction to provide novel perspectives for theoretical supplementation and ferroptosis‐based immunotherapy.MethodsWe retrieved MGST1 expression data via several public data portals. The relationships between MGST1 expression and clinicopathologic characteristics as well as survival time were evaluated via multivariate methods and Kaplan–Meier survival curves. The MGST1‐interacting protein–protein interaction was also established by the STRING website. The TIMER and GEPIA databases were used to illustrate the association between MGST1 expression and infiltrated immune cells. We used the MethSurv website and the UALCAN website to determine the relationship between MGST1 expression and DNA methylation.ResultsMGST1 overexpression in UCEC compared with normal tissues correlates with different histological types, a lack of hormone therapy and poor survival time. MGST1 interacts with several ferroptosis‐related proteins. Overexpression of MGST1 was accompanied by lower levels of NK cell and CD8+ T cell infiltration, higher myeloid‐derived suppressor cell infiltration and different immunocytes with corresponding markers. Hypermethylation and low promoter methylation cooperate to regulate MGST1 expression.ConclusionElevated MGST1 expression is related to tumour development and poor prognosis, as well as dysregulated infiltration of immune cells in UCEC, which can be a potential prognostic indicator and ferroptosis‐based immunotherapy target.

Signal transducer and activator of transcription family is a prognostic marker associated with immune infiltration in endometrial cancer

AbstractBackgroundSignal transducer and activator of transcription (STAT) is a unique protein family that binds to DNA and plays a vital role in regulating major physiological cellular processes. Seven STAT genes have been identified in the human genome. Several studies suggest STAT family members to be involved in cancer development, progression, and metastasis. However, the predictive relationship between STAT family expression and immune cell infiltration in endometrial cancer remains unknown.MethodsWe explored STAT family expression and prognosis in endometrial cancer using various databases. The STRING, GeneMANIA, and DAVID databases, along with GO and KEGG analyses, were used to construct a protein interaction network of related genes. Finally, the TIMER database and ssGSEA immune infiltration algorithm were used to investigate the correlation of STAT family expression with the immune infiltration level in uterine corpus endometrial carcinoma (UCEC).ResultsOur study showed that different STAT family members are differentially expressed in UCEC. STAT1 and STAT2 expression increased at various stages of UCEC, and STAT5A, STAT5B, and STAT6 levels were decreased. STAT3 and STAT4 expression was not significantly different between UCEC and normal tissues. High STAT1 expression may be a prognostic disadvantage of UCEC, and high STAT6 expression may improve UCEC patient prognosis. The STAT family‐associated genes were significantly enriched in signal transduction, protein binding, DNA binding, and ATP binding upon GO analysis. Related genes in the KEGG analysis were mainly enriched in pathways in cancer, viral carcinogenesis, chemokine signaling pathway, JAK/STAT signaling pathway, and regulation of the actin cytoskeleton. In terms of immune infiltration, STAT1 and STAT2 were positively correlated with B, CD8+ T, CD4+ T, and dendritic cells, and neutrophils (p < 0.05). All STAT family members were positively correlated with neutrophils and dendritic cells (p < 0.05). STAT1 and STAT2 showed similar correlations with all immune cell types, whereas STAT1 and STAT6 showed opposite correlations.ConclusionThese findings suggest that the STAT family is a prognostic marker, and the immune infiltration level, a therapeutic target, for endometrial cancer.

Effects of m6A RNA methylation regulators on endometrial cancer

AbstractBackgroundThe modification 6‐methyladenine (m6A) is the most common type in RNA methylation. Our study aims to explore the bioinformatic analysis of m6A in endometrial cancer.MethodsThe expression of 23 m6A RNA methylation regulators was compared through The Cancer Genome Atlas (TCGA) database among 406 endometrial tissue and 19 normal tissue samples. The Wilcoxon test was applied to compare the relationship between the clinicopathological characteristics and expression. Cox regressions were performed to identify the prognostic factors associated with overall survival. Gene ontology (GO) and Gene Set Enrichment Analysis (GSEA) were performed to evaluate the potential pathways.ResultsYTHDF2, HNRNPA2B1, HDRNPA2B1, YTHDF1, FMR1, IGF2BP3, METTL13, RBM15B, IGF2BP1, YTHDF3, YTHDC1, ZC3H13 IGF2BP2, KIAA1429, METTL14, RBMX, FTO, ALKBH5, and METTL16 were significantly abnormally expressed in endometrial cancer tissue samples. Both univariate and multivariate Cox regression analyses indicated that age, grade, and risk score were independent risk factors. High expression of FTO was associated with worse overall survival.ConclusionM6A RNA methylation regulators play vital role in endometrial cancer.

Clinical application of red cell distribution width, mean platelet volume, and cancer antigen 125 detection in endometrial cancer

Abstract Background Red cell distribution width (RDW) and mean platelet volume (MPV) are considered to be associated with tumors. We investigated the diagnostic value of RDW, MPV, and cancer antigen 125 (CA125), alone or in combination, in the diagnosis of endometrial cancer and endometrial hyperplasia. Methods This study included 144 patients with endometrial cancer (stage I: 32; II: 42; III: 48; and IV: 22), 104 patients with endometrial hyperplasia, and 80 healthy control subjects. The whole blood cell parameters were analyzed by a Mindray Blood Cell Analyzer (CAL8000), whereas CA125 was analyzed using an Architect i2000 Analyzer (Abbott). Results Significant differences in RDW, MPV, and CA125 level were observed in the endometrial cancer, endometrial hyperplasia, and control groups ( P  < .05). Red cell distribution width was positively correlated ( r  = .735) whereas MPV was negatively correlated with ( r  = −.736) endometrial cancer staging. The area under the receiver operating characteristic curve of the combined diagnosis of endometrial cancer based on RDW, MPV, and CA125 was 0.924 (95% CI: 0.881‐0.955). The sensitivity and specificity of the combined diagnosis were larger than those of the independent detections involving RDW, MPV, and CA125. Conclusions The combination of RDW, MPV, and CA125 can improve the differential diagnosis of endometrial cancer and endometrial hyperplasia.

Association of polymorphisms in MALAT1 with the risk of endometrial cancer in Southern Chinese women

AbstractBackgroundEndometrial cancer is the most common gynecologic malignancy worldwide. Polymorphisms in MALAT1 have been demonstrated to play critical roles in cancer. However, the roles of MALAT1 polymorphisms in the etiology of endometrial cancer have not been well documented.MethodsWe genotyped three MALAT1 polymorphisms in 249 endometrial cancer cases and 446 cancer‐free female controls using quantitative polymerase chain reaction with TaqMan probes. To estimate the association between MALAT1 polymorphisms (rs591291 C>T, rs664589 C>G, and rs4102217 G>C) and the risk of endometrial cancer, an unconditional logistic regression model was conducted to calculate the odds ratio (OR) and the 95% confidence interval (CI), adjusting for surgery history, menopause, number of deliveries, BMI, and FIGO stage.ResultsWe found that the MALAT1 rs664589 C>G polymorphism was significantly associated with endometrial cancer risk (heterogeneous: adjusted OR = 0.57, 95% CI = 0.34‐0.93, P = .026; homogenous: adjusted OR = 3.74, 95% CI = 1.12‐12.45, P = .032; and recessive: adjusted OR = 4.06, 95% CI = 1.22‐13.48, P = .022). Stratified analysis further demonstrated that the MALAT1 rs664589 C>G polymorphism significantly increased the risk of endometrial cancer susceptibility in patients with no history of surgery, more deliveries, BMI between 25 and 29.9, and FIGO stages II‐III. Compared with the wild‐type GCG haplotype carriers, individuals with CGG haplotypes had a higher risk of developing endometrial cancer.ConclusionThe MALAT1 rs664589 C>G polymorphism was associated with a significant increase in endometrial cancer risk.

Distribution of HPV Types in Cervical Cancer in Pakistan: Implications for Screening and Vaccination Programs

ABSTRACTBackgroundHPV plays a key role in the development of cervical cancer. This study aims to investigate the prevalence of HPV genotypes in patients with Squamous cell carcinoma (SSC) and Adenocarcinoma (ADC) at NORI cancer Hospital Pakistan, with the aim of improving screening and prevention strategies.MethodCervical scrapings were collected from 129 diagnosed cervical cancer patients. HPV typing was performed using a real‐time PCR assay and sequencing.ResultAmong the patients, 73.6% (90/129) were HPV positive. Proportion of HPV positivity was observed within each group. The highest incidence of HPV was observed in the 50–60 years age group (80.9%), followed by the 40‐to‐50‐year group (75.8%). The positivity rate declined in the 60‐to‐70‐year‐old (63.6%) and further in the 70–80 years (62.5%). Eight different HPV subtypes were identified, with HPV 16 being the most prevalent (80.0%), followed by HPV 18 (9.5%), HPV 45 in 2 (2.1%), HPV 31 in 1 (1.1%), HPV 35 in 1 (1.1%), HPV 59 in 1 (1.1%), HPV 66 in 1 (1.1%), and HPV 89 in 1 (1.15). Histologically, 89.2% of the cases were Squamous cell carcinoma (SCC) and 10.8% were Adenocarcinomas. In SCC patients, HPV 16 was found in 80.9% of cases, while in Adenocarcinoma patients, HPV 16 was detected in 66.7% of cases.ConclusionThe prevalence of high‐risk HPV types, both vaccine and non‐vaccine, targeted in Pakistan highlights the urgent need for widespread screening and vaccination programs. Tailored public health strategies are essential to effectively reduce cervical cancer rates and mortality.

METTL3‐mediated m6A modification of lnc RNA RHPN1‐AS1 enhances cisplatin resistance in ovarian cancer by activating PI3K/AKT pathway

AbstractBackgroundCisplatin resistance is a big challenge for ovarian cancer (OC) therapy. The abnormal expression of long noncoding RNAs (lncRNAs) regulated by N6‐methyladenosine (m6A) modification has been confirmed to play the crucial roles in OC. The aim of this study is to explore the regulatory mechanism of lncRNA RHPN1‐AS1 on OC with cisplatin resistance.MethodsThe real‐time reverse transcription‐polymerase chain reaction was carried out to confirm the expression of RHPN1‐AS1 and methyltransferase‐like 3 (METTL3) in OC. The effects of RHPN1‐AS1 on cisplatin‐resistant OC cells were identified by cell functional experiments and animal experiment. Western blotting was performed to detect the effect of RHPN1‐AS1 on PI3K/AKT pathway. Moreover, methylated RNA immunoprecipitation and RNA stability assays confirmed the interaction between RHPN1‐AS1 and METTL3.ResultsRHPN1‐AS1 and METTL3 were confirmed to be overexpressed in OC. After transfecting RHPN1‐AS1 overexpression or RHPN1‐AS1 knockdown vectors into cisplatin‐resistant OC cells, it was found that upregulating RHPN1‐AS1 contributed to cell viability, migration, invasion, and tumor growth in vivo. In addition, RHPN1‐AS1 could enhance the protein levels of PI3K and phosphorylated AKT in cisplatin‐resistant OC cells, and METTL3 could enhance the stability of RHPN1‐AS1 by the m6A modification.ConclusionOverall, this study revealed that METTL3‐mediated m6A modification of RHPN1‐AS1 accelerates cisplatin resistance in OC by activating PI3K/AKT pathway.

hsa_circ_0119412 overexpression promotes cervical cancer progression by targeting miR‐217 to upregulate anterior gradient 2

AbstractBackgroundMounting evidence summarizes that circRNA is closely implicated in the development of numerous cancers. Our study aimed to investigate the role of circ_0119412 whose function was not explored in cervical cancer.MethodsRT‐qPCR analysis was utilized for the expression analysis of circ_0119412, miR‐217, and anterior gradient 2 (AGR2). CCK‐8 assay, transwell assay, and MTT assay were employed to assess cell proliferation, migration, and adhesion, respectively. Animal study was performed to check the role of circ_0119412 in vivo. Bioinformatics analysis was applied to predict the downstream targets of circ_0119412. RIP assay was utilized to examine miRNAs potentially bound by circ_0119412. The interplays between miR‐217 and circ_0119412 or AGR2 were validated by dual‐luciferase reporter assay.Resultscirc_0119412 expression was highly enhanced in cervical tumor tissues and cancer cells. circ_0119412 overexpression aggravated cervical cancer cell proliferation, migration, and adhesion, and its overexpression was also conducive to tumor formation and growth in animal models. AGR2 was upregulated in cervical cancer by the public bioinformatics data. circ_0119412 bound to miR‐217, and miR‐217 bound to AGR 3’UTR. The promoting effects of circ_0119412 overexpression on cancer cell malignant phenotypes were reversed by miR‐217 enrichment. In addition, increased expression of miR‐217 suppressed AGR2 expression, thus weakening the functional effects of AGR2.Conclusioncirc_0119412 functioned as an oncogenic driver to promote the malignant development of cervical cancer by targeting the miR‐217/AGR2 pathway.

RACK1 promotes the occurrence and progression of cervical carcinoma

AbstractBackgroundRACK1 has been identified as a multifunctional cytosolic protein, and plays a pivotal role in multiple biological responses involved in several kinds of tumors, while its effect in cervical cancer has not been well elucidated yet. The study aimed to investigate the role of RACK1 in cervical cancer occurrence and progression.MethodsThe expression of RACK1 in cervical specimens was measured by immunohistochemical staining and Western blot assay. Transgenic mice were used to detect the role of RACK1 in modulating tumorigenesis in vivo. Cervical carcinoma cell lines were used to explore the underlying mechanisms of RACK1 on the behaviors of tumor cells in vitro.ResultsWe found that RACK1 expression was upregulated in cancer tissues compared with adjacent tissues, and its expression was gradually increased from cervictis, and cervical intraepithelial neoplasis (CIN) to carcinoma. Genetic overexpression of RACK1 facilitated tumor formation and growth in nude mice. Mechanism studies disclosed that RACK1 over‐expression prolonged the G0/G1 phase by up‐regulating the expression of cyclinD1, down‐regulating p21 and p27 probably by modulating the phosphorylation of AKT.ConclusionsTaken together, we concluded that RACK1 stimulates tumorigenesis and progression of cervical cancer via modulating the proliferation of tumor cells, implying that targeting RACK1 may serve as a promising method for cervical cancer therapy.

Significantly elevated serum human epididymis protein‐4 in chronic kidney disease patients without ovarian cancer: A large‐scale retrospective study

AbstractBackgroundsHuman epididymis protein‐4 (HE‐4) is a commonly used biomarker for diagnosing ovarian cancer. Elevated HE‐4 has also been observed in various benign conditions including chronic kidney disease (CKD); however, generalizability and statistical power of previous studies have been limited by small sample sizes.Materials and MethodsWe conducted a retrospective study that included 80 pathologically confirmed ovarian cancer patients, 641 CKD patients, and 2661 healthy controls. Serum HE‐4 and several renal function parameters were collected and compared between the three groups. Correlation analysis was conducted to evaluate the relationship between HE‐4 and renal function parameters. A receiver operating characteristic curve was established to evaluate its diagnostic performance.ResultsCKD patients had the highest levels of HE‐4, with a median of 193.00 pmol/L, while the median in ovarian cancer patients was 90.82 pmol/L. HE‐4 levels also increased with CKD progression, and Spearman's rank correlation showed that HE‐4 had a strong correlation with renal function parameters in CKD patients. Furthermore, HE‐4 exhibited a satisfactory diagnostic performance in both differentiating CKD patients and controls as well as stage 2 CKD patients and controls.ConclusionHE‐4 can be used as an alternative biomarker for diagnosing CKD as it is less affected by several preanalytical factors. Nevertheless, in clinical practice, elevated HE‐4 requires taking both CKD and ovarian cancer into consideration.

Persistent AST Elevation in a Patient With Ovarian Cancer: A Rare Diagnostic Challenge

ABSTRACTBackgroundPersistent elevation of aspartate aminotransferase (AST) is commonly indicative of liver injury or disease, but isolated AST elevation without concurrent alanine aminotransferase (ALT) increase is rare and difficult to diagnose. While AST is non‐specific and found in various tissues, its isolated elevation is due to less common conditions, such as macro‐AST, where AST binds with immunoglobulins creating a high‐molecular‐weight complex that affects serum activity.Case DescriptionA 68‐year‐old female with a history of high‐grade serous ovarian cancer (HGSOC) who had persistent isolated AST elevation for several years. Evaluations including physical exams, imaging, and routine liver function tests showed no evidence of hepatic or muscular disease. The polyethylene glycol (PEG) precipitation significantly reduced serum AST activity, confirming the presence of the macro‐enzyme form of AST (macro‐AST).ConclusionThis case highlights the rare and novel occurrence of macro‐AST in a patient with ovarian cancer. It emphasizes the importance of considering macro‐AST in the differential diagnosis of isolated AST elevation, particularly in patients without clear evidence of liver or muscular disease. Recognizing this benign condition can prevent unnecessary diagnostic procedures and anxiety.

Novel long noncoding RNA LINC02323 promotes cell growth and migration of ovarian cancer via TGF‐β receptor 1 by miR‐1343‐3p

AbstractBackgroundThis study was aimed at investigating the effects of long noncoding RNA (lncRNA) LINC02323 in ovarian cancer and its possible mechanism.MethodsMicroarray analysis and QPCR were utilized to identify lncRNA LINC02323 expression in patients with ovarian cancer. MTT assay was used for analysis of ovarian cancer cell proliferation. Western blot was utilized to investigate its possible mechanism.ResultsIn patients with ovarian cancer, lncRNA LINC02323 expression was up‐regulated and miR‐1343‐3p expression was down‐regulated. Over‐expression of lncRNA LINC02323 promoted cell growth and reduced LDH activity levels in vitro model by suppression of miR‐1343‐3p expression. Down‐regulation of lncRNA LINC02323 reduced cell growth and increased LDH activity levels in vitro model by induction of miR‐1343‐3p expression. Over‐expression of miR‐1343‐3p reduced cell growth and reduced LDH activity levels in vitro model by suppression of TGF‐β receptor. Down‐regulation of miR‐1343‐3p promoted cell growth and reduced LDH activity levels in vitro model by induced of TGF‐β receptor.ConclusionOur findings show that Novel long noncoding RNA LINC02323 promotes cell growth of ovarian cancer via TGF‐β receptor 1 by miR‐1343‐3p.

The prognostic value of the lysyl oxidase family in ovarian cancer

AbstractBackgroundOur study intended to evaluate the prognostic value of lysyl oxidase (LOX) and its four relevant members, the lysyl oxidase–like genes (LOXL1‐4), in ovarian cancer (OC) patients.Material and MethodsThe Kaplan‐Meier plotter (KM plotter) database was used to investigate the prognostic power of the LOX family for OC patients. Overall survival (OS) and progression‐free survival (PFS) were the clinical endpoints. The prognostic roles of the LOX family in OC patients were also analyzed according to various clinicopathological characteristics, including histological subtypes, clinical stages, pathological grades, and chemotherapeutic treatments.ResultsOverexpression of LOX, LOXL1, LOXL2, and LOXL3 mRNA indicated poor OS and PFS in OC patients, particularly in serous and grade II + III OC patients. Overexpression of LOXL4 mRNA resulted in worse PFS in OC patients. Overexpression of LOX and LOXL1 mRNA showed worse OS and PFS in stage III + IV OC patients, and overexpression of LOXL3 mRNA indicated worse OS and PFS in stage I + II OC patients. Overexpression of LOX, LOXL3, and LOXL4 mRNA indicated worse OS and PFS among OC patients who received platinum, taxol, and taxol + platinum chemotherapy. Overexpression of LOXL1 and LOXL2 mRNA was related to lower OS and PFS in OC patients who received platinum chemotherapy.ConclusionLOX, LOXL1, LOXL2, and LOXL3 may become potential predictive markers for negative outcomes in OC patients. Moreover, the LOX family can serve as new molecular predictors for the efficiency of platinum‐based chemotherapy in OC patients.

Eukaryotic initiation factor 3B is overexpressed and correlates with larger tumor size, advanced FIGO stage, and shorter overall survival in epithelial ovarian cancer patients

Abstract Background This study aimed to detect the eukaryotic initiation factor 3B (EIF3B) expression and explore its correlation with clinical features and prognosis in epithelial ovarian cancer (EOC) patients. Methods A total of 230 primary EOC patients underwent surgery treatment were retrospectively reviewed. Immunohistochemical (IHC) assay was used to determine EIF3B expression in tumor and adjacent tissue specimens of all patients. According to the total IHC score, the expression of EIF3B was classified as low expression and high expression, and the latter was further divided into 3 grades: high+, high++, and high+++ expressions. Overall survival (OS) was calculated. Results Eukaryotic initiation factor 3B expression was increased in tumor tissue compared with adjacent tissue. Tumor EIF3B high expression correlated with larger tumor size (>10 cm), lymphatic metastasis, and advanced International Federation of Gynecology and Obstetrics stage (FIGO) (III/IV). Besides, OS was decreased in patients with tumor EIF3B high expression compared with patients with tumor EIF3B low expression, and further analysis showed that the OS was shortest in patients with tumor EIF3B high+++ expression, followed by patients with tumor EIF3B high++ expression and patients with tumor EIF3B high + expression, and the longest in patients with tumor EIF3B low expression. Additionally, higher tumor EIF3B expression, peritoneal cytology (positive), ascites volume (>100 mL), differentiation (poor vs. well/moderate), tumor size (>10 cm), FIGO stage (III/IV vs. I/II), and cancer antigen 125 (>1000 U/mL) independently predicted shorter OS. Conclusion Eukaryotic initiation factor 3B exhibits a clinical value for monitoring disease progression and predicting prognosis in EOC patients.

Aberrant expression of ADAM9 in ovarian cancer and its clinical significance

AbstractBackgroundThe oncogene a disintegrin and metalloproteinase 9 (ADAM9) was up‐regulated in ovarian cancer tissues, and the present study aims to explore the potential diagnostic and prognostic value of ADAM9 in ovarian cancer (OC).MethodsA total of 30 paired fresh OC tumor tissues and the paired‐adjacent normal tissue, and 90 formalin‐fixed paraffin‐embedded (FFPE) OC samples and adjacent normal tissue were collected. The expression of OC in FFPE samples was examined by immunohistochemical methods, and the mRNA expression of ADAM9 in fresh tumor samples was examined by RT‐qPCR methods. Receiver operating characteristics curve was drawn to analyze the potential diagnostic value of ADAM9. Kaplan‐Meier survival analysis was performed to compare the overall survival (OS) and disease‐free survival (DFS) of the ADAM9 positive and negative OC patients.ResultsThe positive rate of ADAM9 in FFPE OC tumor tissue was markedly higher than in the non‐tumorous tissue (61/90 vs 47/90), and increased expression level of ADAM9 may associate with higher histological grade, advanced Figo stage and increased risk of metastasis; moreover, the mRNA expression of ADAM9 was also increased in OC tissue compared with the normal tissue (P < .001), and results of ROC analysis suggested that ADAM9 is a sensitive marker for the diagnosis of OC( AUC 0.8389, 95% confidence interval 0.7333 to 0.9445); finally, increased expression of ADAM9 may indicate decreased OS (P = .004) and DFS (P = .014) of the patients.ConclusionA disintegrin and metalloproteinase 9 was up‐regulated in OC, and ADAM9 may serve as potential diagnostic and prognostic marker for the diagnosis and treatment of OC.

LncRNA LIFR‐AS1 overexpression suppressed the progression of serous ovarian carcinoma

AbstractBackgroundSerous ovarian carcinoma (SOC) is a common malignant tumor in female reproductive system. Long noncoding RNA (lncRNA) LIFR‐AS1 is a tumor suppressor gene in colorectal cancer, but its effect and underlying mechanism in SOC are still unclear. Therefore, this study focuses on unveiling the regulatory mechanism of LIFR‐AS1 in SOC.MethodsThe relationship between LIFR‐AS1 expression and prognosis of SOC patients was analyzed by TCGA database and Starbase, and then, the LIFR‐AS1 expression in SOC tissues and cells was detected by quantitative real‐time PCR (qRT‐PCR) and in situ hybridization (ISH). Besides, the relationship between LIFR‐AS1 and clinical characteristics was analyzed. Also, the effects of LIFR‐AS1 on the biological behaviors of SOC cells were measured by Cell Counting Kit‐8, colony formation, and wound‐healing and Transwell assays, respectively. Western blot and qRT‐PCR were employed to determine the protein expressions of genes related to proliferation (PCNA), apoptosis (cleaved caspase‐3), epithelial‐mesenchymal transition (E‐cadherin, N‐cadherin, and Snail).ResultsLIFR‐AS1 was lowly expressed in SOC, which was correlated with the poor prognosis of SOC patients. Low expression of LIFR‐AS1 in SOC was associated with the tumor size, clinical stage, lymph node metastasis, and distant metastasis. LIFR‐AS1 overexpression promoted the expressions of cleaved caspase‐3 and E‐cadherin while suppressing the malignant behaviors (proliferation, migration, and invasion) of SOC cells, the expressions of PCNA, N‐cadherin, and Snail. Besides, silencing LIFR‐AS1 exerted the effects opposite to overexpressed LIFR‐AS1.ConclusionLIFR‐AS1 overexpression inhibits biological behaviors of SOC cells, which may be a new therapeutic method.

A case of ovarian Teratoma with nephroblastoma presenting abdomen metastasis

AbstractBackgroundTeratoma with nephroblastoma (TWN) is an extremely rare condition. Since 1984, only 45 reported cases have been identified. To our knowledge, there have been only two cases of TWN of ovarian origin.Case presentationWe described a case of ovarian TWN who presented to us with painless abdominal masses 6 months after undergoing right ovarian cystectomy. The tumor had spread to the abdomen due to spontaneous rupture of the ovarian cyst and failure to undergo chemotherapy. Microscopically, the ovarian mass exhibited the typical components of a mature cystic teratoma. The tumors found in both the ovary and abdomen contained the nephroblastoma components and were strongly positive for WT‐1. The patient was advised to undergo chemotherapy and she was lost to follow‐up.ConclusionA careful histological examination is necessary for an accurate diagnosis, which is based on morphology and extensive immunohistochemical studies. According to the literature, surgical excision alone seems reasonable as the prognosis of TWN is considered to be good. However, due to the spontaneous rupture of the ovarian cyst, chemotherapy of the patient after the first surgery was necessary in our case. Therefore, additional case studies are needed to clarify the standardized treatment of TWN.

Integrated weighted gene co‐expression network analysis reveals biomarkers associated with prognosis of high‐grade serous ovarian cancer

AbstractBackgroundOvarian cancer is the gynecologic tumor with the highest fatality rate, and high‐grade serous ovarian cancer (HGSOC) is the most common and malignant type of ovarian cancer. One important reason for the poor prognosis of HGSOC is the lack of effective diagnostic and prognostic biomarkers. New biomarkers are necessary for the improvement of treatment strategies and to ensure appropriate healthcare decisions.MethodsTo construct the co‐expression network of HGSOC samples, we applied weighted gene co‐expression network analysis (WGCNA) to assess the proteomic data obtained from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), and module‐trait relationship was then analyzed and plotted in a heatmap to choose key module associated with HGSOC. Subsequently, hub genes with high connectivity in key module were identified by Cytoscape software. Furthermore, the biomarkers were selected through survival analysis, followed by evaluation using the relative operating characteristic (ROC) analysis.ResultsA total of 9 modules were identified by WGCNA, and module‐trait analysis revealed that the brown module was significantly associated with HGSOC (cor = 0.7). Ten hub genes with the highest connectivity were selected by protein‐protein interaction analysis. After survival and ROC analysis, ALB, APOB and SERPINA1 were suggested to be the biomarkers, and their protein levels were positively correlated with HGSOC prognosis.ConclusionWe conducted the first gene co‐expression analysis using proteomic data from HGSOC samples, and found that ALB, APOB and SERPINA1 had prognostic value, which might be applied for the treatment of HGSOC in the future.

A combined biomarker panel shows improved sensitivity and specificity for detection of ovarian cancer

AbstractBackgroundCombined biomarkers can improve the sensitivity and specificity of ovarian cancer (OC) diagnosis and effectively predict patient prognosis. This study explored the diagnostic and prognostic values of serum CCL18 and CXCL1 antigens combined with C1D, FXR1, ZNF573, and TM4SF1 autoantibodies in OC.MethodsCCL18 and CXCL1 monoclonal antibodies and C1D, FXR1, ZNF573, and TM4SF1 antigens were coated with microspheres. Logistic regression was used to construct a serum antigen‐antibody combined detection model; receiver‐operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of the model; and the Kaplan‐Meier method and Cox regression models were used for survival analysis to evaluate the prognosis of OC. Data from The Cancer Genome Atlas (TCGA) and Genotype‐Tissue Expression (GTEx) projects and online survival analysis tools were used to evaluate prognostic genes for OC. The CIBERSORT immune score was used to explore the factors influencing prognosis and their relationship with tumor‐infiltrating immune cells.ResultsThe levels of each index in the blood samples of patients with OC were higher than those of the other groups. The combined detection model has higher specificity and sensitivity in the diagnosis of OC, and its diagnostic efficiency is better than that of CA125 alone and diagnosing other malignant tumors. CCL18 and TM4SF1 may be factors affecting the prognosis of OC, and CCL18 may be related to immune‐infiltrating cells.ConclusionsThe serum antigen‐antibody combined detection model established in this study has high sensitivity and specificity for the diagnosis of OC.

A potential disease monitoring and prognostic biomarker in cervical cancer patients: The clinical application of circular RNA_0018289

Abstract Objective This study aimed to investigate the tumor circular RNA_0018289 (circ_0018289) expression and its correlation with clinical characteristics as well as survival profiles in cervical cancer patients. Methods A hundred and ninety‐two cervical cancer patients who received surgical resection were recruited in this prospective study. Tumor tissue and paired adjacent tissue were obtained during the surgery, in which circ_0018289 expression was detected by reverse transcription quantitative polymerase chain reaction. Disease‐free survival (DFS) and overall survival (OS) were recorded. Results Circ_0018289 expression was upregulated in tumor tissue compared with paired adjacent tissue ( P  < .001), and receiver operative characteristic curve disclosed its good value for separating tumor tissue from adjacent tissue with an area under curve of 0.907 (95% CI: 0.879‐0.935). Additionally, tumor circ_0018289 expression was positively associated with tumor size ( P  = .009), lymph node metastasis ( P  = .005) and Federation International of Gynecology and Obstetrics stage ( P  = .005). The DFS ( P  = .005) and OS ( P  = .015) were both worse in patients with circ_0018289 high expression compared to patients with circ_0018289 low expression. Meanwhile, in patients with circ_0018289 high expression, DFS and OS were the longest in patients with high+ expression followed by patients with high++ expression, and the shortest in patients with high+++ expression. Moreover, circ_0018289 high expression could independently predict worse DFS in the total cervical cancer patients ( P  = .042). Conclusion Circ_0018289 could serve as a potential disease monitoring and prognostic biomarker in cervical cancer patients.

Relevance research between the expression of p16INK4a, Notch1, and hTERC genes: The development of HPV16‐positive cervical cancer

AbstractBackgroundGLOBOCAN 2018 latest data show cervical cancer ranks fourth in morbidity and mortality among women. Many genes in cervical lesions differ in sensitivity and specificity. However, the diagnostic molecules for early cervical cancer are not very clear. This paper screens biomarkers for early molecular diagnosis of Mongolian patients with cervical cancer.MethodsImmunohistochemical SP method was used to detect the expression of p16INK4a and Notch1 protein in paraffin sections of 226 Mongolian patients with HPV16‐positive cervical lesions after pathological examination, and 100 of them were randomly selected by fluorescence in situ hybridization to detect hTERC gene. The HPV16‐binding human cervical cancer SiHa cell line was used to silence the expression of HPV16 E6/E7 gene by RNA interference, and the expression of p16INK4a, Notch1, and hTERC genes and protein expression levels were detected by RT‐PCR and Western blot.ResultsThe positive expression rates of p16INK4a, Notch1, and hTERC genes in HPV16‐positive cervical cancer, CIN‐III, CIN‐II, CIN‐I, uterine leiomyoma, and chronic cervicitis were significantly different (P < .05); the positive expression rates of the three genes were also significantly different in the same type of cervical lesions (P < .05); RNA interference can effectively inhibit HPV16 E6/E7, p16INK4a and Notch1 gene expression, but has no effect on hTERC gene expression.ConclusionThe p16INK4a gene can be used as a biomarker for early screening of cervical cancer, and the hTERC gene can be used to confirm the clinical diagnosis of cervical cancer.

Expression of the HOXA gene family and its relationship to prognosis and immune infiltrates in cervical cancer

AbstractBackgroundThe homeobox A cluster (HOXA) gene family is participated in multiple biological functions in human cancers. To date, little is known about the expression profile and clinical significance of HOXA genes in cervical cancer.MethodsWe downloaded RNASeq data of cervical cancer from The Cancer Genome Atlas (TCGA) database. The difference in HOXA family expression was analyzed using independent samples t test. Cox proportional hazard regression analysis was used to assess the effect of HOXA family expression on survival, and a nomogram predicting survival was generated. We assessed the infiltration difference in immune cells and expression difference of immunity biomarkers between two groups with different expression level of HOXA genes through Immune Cell Abundance Identifier (ImmuCellAI) and independent samples t test, respectively.ResultsOur results showed that the HOXA1 gene was upregulated, while the HOXA10 and HOXA11 were downregulated in cervical cancer. Downregulation of HOXA1 was related to a poor outcome for cervical cancer patient. We also identified a significantly increased abundance of T helper 2 cells (Th2) and higher expression of PD‐L1 in cervical cancer patients with lower expression of HOXA10 and HOXA11. The gene set enrichment analysis (GSEA) results indicated that HOXA1 and HOXA11 were involved in immune responses pathways and participated in the activation of a variety of classic signaling pathways related to the progression of human cancer.ConclusionThis study comprehensively analyzed different HOXA genes applying public database to determine their expression patterns, potential diagnostic, prognostic, and treatment values in cervical cancer.

miR‐92a promotes cervical cancer cell proliferation, invasion, and migration by directly targeting PIK3R1

AbstractObjectiveTo clarify the role of miR‐92a in regulating the malignant progression of cervical cancer and its specific molecular mechanism.MethodsqRT‐PCR was used to detect the differential expression of miR‐92a in cervical cancer and adjacent tissues. The effects of overexpression of miR‐92a on the proliferation, migration, and invasion of HeLa and SiHa cells were tested. Luciferase assays and rescue experiments were used to investigate the regulatory mechanism of miR‐92a on its downstream gene PIK3R1 and their interaction in the progression of cervical cancer.ResultsmiR‐92a was significantly up‐regulated in cervical cancer tissues. Overexpression of miR‐92a significantly increased the ability of cervical cancer cells to proliferate, migrate, and invade. PIK3R1 was identified as a downstream gene of miR‐92a. In cervical cancer tissues, PIK3R1 was found to be down‐regulated and negatively correlated with the level of miR‐92a. Overexpression of PIK3R1 reversed the promotional effect of overexpressed miR‐92a on the proliferation, migration, and invasion of cervical cancer.ConclusionmiR‐92a is up‐regulated in cervical cancer tissues. miR‐92a promotes the malignant development of cervical cancer by negatively regulating PIK3R1.

CCT6A may act as a potential biomarker reflecting tumor size, lymphatic metastasis, FIGO stage, and prognosis in cervical cancer patients

AbstractObjectiveChaperonin‐containing tailless complex polypeptide subunit 6A (CCT6A) is a critical regulator and newly identified clinical biomarker of several cancers, while its correlation with the clinical characteristics and prognosis of cervical cancer patients is unclear. Therefore, this study aimed to explore this issue.MethodsChaperonin‐containing tailless complex polypeptide subunit 6A expression in tumor and tumor‐adjacent tissues from 198 cervical cancer patients who underwent resection were detected by immunohistochemistry assay and reverse transcription‐quantitative polymerase chain reaction. Besides, the clinicopathological features and survival data of cervical cancer patients were collected.ResultsChaperonin‐containing tailless complex polypeptide subunit 6A protein and mRNA levels were both increased in tumor tissues compared with tumor‐adjacent tissues (both p < 0.001). Receiver operating characteristic curves showed that CCT6A protein (AUC: 0.774, 95% CI: 0.729–0.819) and mRNA levels (AUC: 0.904, 95% CI: 0.874–0.934) well discriminated tumor tissues from tumor‐adjacent tissues. Besides, correlation analyses found that CCT6A protein and mRNA levels were positively correlated with lymph node metastasis and FIGO stage (all p < 0.05), apart from which CCT6A mRNA level was also positively associated with tumor size (p = 0.032). In addition, CCT6A protein and mRNA levels were negatively correlated with accumulating disease‐free survival (both p < 0.05); meanwhile CCT6A mRNA level was negatively associated with accumulating overall survival as well (p = 0.010).ConclusionChaperonin‐containing tailless complex polypeptide subunit 6A is elevated in tumor tissues, and its high expression associates with larger tumor size, lymph node metastasis, higher FIGO stage, and worse prognosis in cervical cancer patients.

CircRNA hsa_circ_0018289 exerts an oncogenic role in cervical cancer progression through miR‐1294/ICMT axis

AbstractBackgroundcircRNA hsa_circ_0018289‐mediated growth and metastasis of CC cells were investigated, as well as the mechanistic pathway.MethodsQuantitative real‐time reverse transcription‐polymerase chain reaction (qRT‐PCR) was carried out to examine the expression of hsa_circ_0018289, microRNA (miR)‐1294, and isoprenylcysteine carboxyl methyltransferase (ICMT). CC cell proliferation, migration, and invasion were evaluated by 5‐ethynyl‐2’‐deoxyuridine (EdU) incorporation, colony formation, transwell assays, Western blot analysis of ICMT, and glycolysis‐associated proteins. Dual‐luciferase reporter or RNA pull‐down analysis of the target interaction between miR‐1294 and hsa_hsa_circ_0018289 or ICMT. Xenograft model assay was implemented to assess the role of hsa_circ_0018289 in vivo. Immunofluorescence (IHC) was employed to detect the level of Ki‐67.ResultsHsa_circ_0018289 was elevated in CC tissues and cells, its deficiency could repress growth, metastasis, and glycolysis of CC cells in vitro, as well as hamper tumor growth in vivo. Hsa_circ_0018289 sponged miR‐1294 while miR‐1294 bound with ICMT, and the inhibition of miR‐1294 or addition of ICMT could partially relieve the effect caused by hsa_circ_0018289 depletion.ConclusionHsa_circ_0018289 contributes to malignant development by regulating the miR‐1294/ICMT axis, affording novel insight into CC therapy.

E2F4 may be a core transcription factor in the lncRNA‐TF regulatory network in cervical cancer

AbstractBackgroundCervical cancer is the most common gynecological cancer worldwide and is associated with high morbidity and mortality. Despite improvements in therapeutic strategies, the network regulation mechanism remains unclear and the treatment effect is not satisfactory. Therefore, there is a need to continue studying the mechanism of cervical cancer to explore effective gene targets and precise targeted therapy drugs.MethodsFirst, three paired tissues (cancer tissues and noncancerous tissues) from patients with cervical squamous cell carcinoma were collected, grouped, and analyzed by microarray. Second, differentially expressed mRNAs (DEMs) and differentially expressed lncRNAs (DELs) (|fold change| ≥ 2 and p < 0.05) between the two groups were screened. For DEMs, functional annotation and pathway analysis were performed using DAVID. Functional prediction of DELs was then performed and their cis‐regulatory and trans‐regulatory networks were explored.ResultsFunction prediction of DELs (both up‐regulated and down‐regulated) shows that the highest frequency Cellular Component (CC) item is cytosol, the highest frequency Molecular function (MF) item is mitotic cell cycle and the highest frequency Biological Process (BP) item is protein binding. Through cis‐regulation analysis of DELs, the cis‐regulatory relationship of 96 DELs was predicted. The lncRNA‐trans‐regulation network analysis suggested that E2F4 may be the core transcription factor in the lncRNA‐TF regulatory network in cervical cancer.ConclusionsThe lncRNA‐TF regulatory network plays an important role in the occurrence and progression of cervical cancer, and E2F4 may be a critical transcription factor in the regulatory network.