Yan Li

LncRNA LINC00261 associates with chemoresistance and clinical prognosis in patients with epithelial ovarian cancer

AbstractObjectiveThe purpose of this experiment is to explore the role of long intergenic noncoding RNA 261 (LINC00261) gene in the chemoresistance and clinical prognosis of epithelial ovarian cancer (EOC).MethodsWe used matrix‐assisted laser desorption ionization time‐of‐flight (MALDI‐TOF) mass spectrometry to detect the methylation levels of the LINC00261 promoter region in EOC patient specimens. The expression levels of LINC00261, miR‐545‐3p, and MT1M in EOC patients were evaluated by quantitative real‐time reverse transcriptase PCR (RT‐qPCR). Spearman's correlation analysis was used for relevance analyses and clinical prognosis was counted by Kaplan–Meier analysis. Stable overexpressed LINC00261 SKOV3 cells were established to test the influence of LINC00261 on proliferation, platinum sensitivity, migration, and invasion.ResultsThe promoter region methylation level of the LINC00261 was hypermethylated and LINC00261 was significantly downregulated in platinum‐resistant EOC tissues. The methylation level of LINC00261was significantly negative correlated with its RNA expression in EOC. Moreover, hypermethylation and lower expression of LINC00261 in EOC patients were related to shorter progression‐free survival (PFS) and overall survival (OS). Furthermore, Spearman's correlation analysis showed that the expression of miR‐545‐3p had a negative relevance with LINC00261. According to the website prediction, MT1M might be the downstream target gene of LINC00261. Expression of MT1M was negatively correlated with miR‐545‐3p and positively with LINC00261 in EOC tissues. And lower MT1M mRNA expression was correlated with chemotherapy resistance and worse prognosis. In vitro, overexpression of LINC00261 could inhibit cisplatin resistance, proliferation, and suppression of migration and invasion in SKOV3 cells.ConclusionsThis research indicates that the aberrant hypermethylation and low expression of LINC00261 were associated with platinum resistance and adverse outcomes in EOC patients.

Short video platforms as sources of health information about cervical cancer: A content and quality analysis

BackgroundThe development of short popular science video platforms helps people obtain health information, but no research has evaluated the information characteristics and quality of short videos related to cervical cancer. The purpose of this study was to evaluate the quality and reliability of short cervical cancer-related videos on TikTok and Kwai.MethodsThe Chinese keyword "cervical cancer" was used to search for related videos on TikTok and Kwai, and a total of 163 videos were ultimately included. The overall quality of these videos was evaluated by the Global Quality Score (GQS) and the modified DISCERN tool.ResultsA total of 163 videos were included in this study, TikTok and Kwai contributed 82 and 81 videos, respectively. Overall, these videos received much attention; the median number of likes received was 1360 (403–6867), the median number of comments was 147 (40–601), and the median number of collections was 282 (71–1296). In terms of video content, the etiology of cervical cancer was the most frequently discussed topic. Short videos posted on TikTok received more attention than did those posted on Kwai, and the GQS and DISCERN score of videos posted on TikTok were significantly better than those of videos posted on Kwai. In addition, the videos posted by specialists were of the highest quality, with a GQS and DISCERN score of 3 (2–3) and 2 (2–3), respectively. Correlation analysis showed that GQS was significantly correlated with the modified DISCERN scores (p<0.001).ConclusionIn conclusion, the quality and reliability of cervical cancer-related health information provided by short videos were unsatisfactory, and the quality of the videos posted on TikTok was better than that of videos posted on Kwai. Compared with those posted by individual users, short videos posted by specialists provided higher-quality health information.

DNA methylome profiling identifies novel methylated genes in epithelial ovarian cancer patients with platinum resistance

AbstractAimPlatinum‐based chemotherapy is widely used for epithelial ovarian cancer (EOC). As high as 20–25% of EOC patients will not respond to the initial chemotherapy. Accumulated evidences have implied that DNA methylation may serve as a potential bio‐marker for chemotherapy‐resistant phenotypic screening; however, the pattern underlying primary platinum resistance remains unclear.MethodsReduced representation bisulfite sequencing (RRBS) analysis was performed to identify differences in methylation status between primary platinum‐resistant patients Progression free survival (PFS) (PFS < 6 months, n = 8) and extreme sensitive patients (PFS ≥ 24 months, n = 8). The Qubit 3.0 Fluorometer was used for the quantification of RRBS library. The RRBS library was sequenced on Illumina HiSeq2500 sequencer as 50 bp paired‐end reads.ResultsAfter screening, 94 valid hyper‐/hypo‐methylated regions were identified to be located within 94 gene promoter and exon regions (adjusted q ≤ 0.5), which were primarily associated with cell–cell adhesion, B cell activation and lymphocyte activation according to GO analysis. The 19 differentially methylated regions (DMR) located in the promoter region including TRC‐GCA11‐1, LOC105370912, ANO7P1, DHX4,MSH2, CDCP2, CCNL1, ARHGAP42P2, PRDM13, LOC101928344, USP29, ZIC5,IL1RAPL1, EVX2, ABR, MGRN1, UBALD1, LINC00261, and ISL2 were identified according to the order of P‐values from low to high, of which MSH2, LINC00261, MGRN1, ZIC5, EVX2, CCNL1, and DHX40 were presented to play a variety of roles in cancers process based on the previous studies.ConclusionDNA methylome profiling based on RRBS assay is an effective method for screening aberrantly methylated genes in primary platinum‐resistant patients, which may serve as a potential epigenetic bio‐marker for the prediction of primary platinum resistance.

Identification of Specific Cell Subpopulations and Marker Genes in Ovarian Cancer Using Single‐Cell RNA Sequencing

Objective. Ovarian cancer is the deadliest gynaecological cancer globally. In our study, we aimed to analyze specific cell subpopulations and marker genes among ovarian cancer cells by single‐cell RNA sequencing (RNA‐seq). Methods. Single‐cell RNA‐seq data of 66 high‐grade serous ovarian cancer cells were employed from the Gene Expression Omnibus (GEO). Using the Seurat package, we performed quality control to remove cells with low quality. After normalization, we detected highly variable genes across the single cells. Then, principal component analysis (PCA) and cell clustering were performed. The marker genes in different cell clusters were detected. A total of 568 ovarian cancer samples and 8 normal ovarian samples were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes were identified according to ∣log2fold change (FC) | >1 and adjusted p value <0.05. To explore potential biological processes and pathways, functional enrichment analyses were performed. Furthermore, survival analyses of differentially expressed marker genes were performed. Results. After normalization, 6000 highly variable genes were identified across the single cells. The cells were divided into 3 cell populations, including G1, G2M, and S cell cycles. A total of 1,124 differentially expressed genes were identified in ovarian cancer samples. These differentially expressed genes were enriched in several pathways associated with cancer, such as metabolic pathways, pathways in cancer, and PI3K‐Akt signaling pathway. Furthermore, marker genes, STAT1, ANP32E, GPRC5A, and EGFL6, were highly expressed in ovarian cancer, while PMP22, FBXO21, and CYB5R3 were lowly expressed in ovarian cancer. These marker genes were positively associated with prognosis of ovarian cancer. Conclusion. Our findings revealed specific cell subpopulations and marker genes in ovarian cancer using single‐cell RNA‐seq, which provided a novel insight into the heterogeneity of ovarian cancer.

Clinicopathological analysis of primary carcinoid tumour of the ovary arising in mature cystic teratomas

Objective To investigate the clinicopathological features, diagnosis and differential diagnosis of patients with primary ovarian carcinoid tumours arising in mature cystic teratomas. Methods This retrospective case series analysed the data from patients with primary ovarian carcinoid tumours arising in mature cystic teratomas. Results The study enrolled four patients. Histopathological analysis of the tumours identified the following subtypes: insular ( n = 1), trabecular ( n = 1) and strumal ( n = 2). All four primary ovarian carcinoid tumours originated from a mature teratoma. The morphology of the primary ovarian carcinoids was similar to other neuroendocrine tumours. Strumal carcinoids were composed of different proportions of thyroid tissue intimately admixed with carcinoid tumour. Tumour tissue was arranged in insular and/or trabecular patterns. The nucleus of tumour cells displayed exquisite chromatin without obvious mitotic figures. Tumour tissues were positively stained for neuroendocrine markers chromogranin A, synaptophysin and CD56 to varying degrees. Strumal carcinoid tumours were cytokeratin 19 positive and thyroid transcription factor 1 negative. No recurrence or metastasis occurred during follow-up (12–71 months). Conclusion Primary ovarian carcinoid tumours arising in mature cystic teratomas are rare. Diagnosis and differential diagnosis should be confirmed by clinical features, histopathological characteristics and specific immunophenotyping.

Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy Improves Survival with Acceptable Safety for Advanced Ovarian Cancer: A Clinical Study of 100 Patients

Background . The mainstay of treatment for advanced ovarian cancer is debulking surgery followed by chemotherapy that includes carboplatin and paclitaxel, but the prognosis is poor. This study is aimed at evaluating the efficacy and safety of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) as first‐line surgical treatment in patients with advanced ovarian cancer (AOC). Methods . FIGO stage III/IV AOC patients underwent CRS+HIPEC as first‐line surgical treatment at our center from December 2007 to January 2020. The primary endpoint was survival, and the secondary endpoint was safety. Results . Among 100 patients, the median Karnofsky performance status (KPS) score was 80 (50‐100), median peritoneal cancer index (PCI) was 19 (1‐39), median completeness of cytoreduction (CC) score was 1 (0‐3), number of organ regions removed was 4 (3‐9), number of peritoneal regions removed was 4 (1‐9), and number of anastomoses was 1 (0‐4). The median follow‐up was 36.8 months; 75 (75.0%) patients were still alive, and 25 (25.0%) had died. The median overall survival (mOS) was 87.6 (95% CI: 72.1‐103.0) months, and the 1‐, 2‐, 3‐, 4‐, and 5‐year survival rates were 94.1%, 77.2%, 68.2%, 64.2%, and 64.2%, respectively. Univariate analysis showed that better mOS correlated with an age ≤, KPS ≥ 80, ascites ≤ 1000 ml, PCI < 19, and CC score 0‐1. Multivariate Cox analysis showed that CC was an independent factor for OS; patients who underwent CRS with a CC score 0‐1 had a mPFS of 67.8 (95% CI: 48.3‐87.4) months. The perioperative serious adverse event and morbidity rates were 4.0% and 2.0%, respectively. Conclusions . CRS+HIPEC improves survival for AOC patients with acceptable safety at experienced high‐volume centers. Stringent patient selection and complete CRS are key factors for better survival.

Screening and Identification of an Immune‐Associated lncRNA Prognostic Signature in Ovarian Carcinoma: Evidence from Bioinformatic Analysis

Backgrounds. The dysregulated long noncoding RNAs (lncRNAs) have been described to be crucial regulators in the progression of ovarian carcinoma. The infiltration status of immune cells is also related to the clinical outcomes in ovarian carcinoma. The present research is aimed at constructing an immune‐associated lncRNA signature with potential prognostic value for ovarian carcinoma patients. Methods. We obtained 379 ovarian carcinoma cases with available clinical data and transcriptome data from The Cancer Genome Atlas database to evaluate the infiltration status of immune cells, thereby generating high and low immune cell infiltration groups. According to the expression of the immune‐associated lncRNA signature, the risk score of each case was calculated. The high‐ and low‐risk groups were classified using the median risk score as threshold. Results. A total of 169 immune‐associated lncRNAs that differentially expressed in ovarian carcinoma were included. According to the Lasso regression analysis and Cox univariate and multivariate analyses, 5 immune‐associated lncRNAs, including AC134312.1, AL133467.1, CHRM3‐AS2, LINC01722, and LINC02207, were identified as a predictive signature with significant prognostic value in ovarian carcinoma. The following Kaplan‐Meier analysis, ROC analysis, and Cox univariate and multivariate analyses further suggested that the predicted signature may be an independent prognosticator for patients with ovarian carcinoma. The following gene set enrichment analysis showed that this 5 immune‐associated lncRNAs signature was significantly related to the hedgehog pathway, basal cell carcinoma, Wnt signaling pathway, cytokine receptor interaction, antigen processing and presentation, and T cell receptor pathway. Conclusion: This study suggested a predictive model with 5 immune‐associated lncRNAs that has an independent prognostic value for ovarian carcinoma patients.

SP1-induced lncRNA MCF2L-AS1 promotes cisplatin resistance in ovarian cancer by regulating IGF2BP1/IGF2/MEK/ERK axis

Cisplatin resistance is a huge problem encountered in ovarian cancer treatment. Our study probed the roles and the underlying mechanisms of lncRNA MCF2L-AS1 in ovarian cancer cisplatin-resistance. SKOV3 and IGROV-1 cells were subjected to gradually increasing concentrations of cisplatin to construct ovarian cancer cisplatin-resistance cells. Cell proliferation was evaluated by cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and PI staining. The relationships between SP1, MCF2L-AS1 and insulin-like growth factor-2 mRNA binding protein 1 (IGF2BP1) were verified by RNA pull-down, RIP, ChIP and dual-luciferase reporter gene assay, respectively. Tumor xenograft experiment was employed to evaluate the effects of MCF2L-AS1 silencing on ovarian cancer cisplatin-resistance in vivo. TUNEL staining and immunohistochemistry were performed in tumor tissue. MCF2L-AS1 and IGF2BP1 were upregulated in cisplatin-resistant cells. MCF2L-AS1 silencing suppressed cell proliferation of cisplatin-resistant cells, while promoted the apoptosis, suggesting that MCF2L-AS1 knockdown suppressed ovarian cancer cells cisplatin-resistance. Meanwhile, MCF2L-AS1 silencing enhanced cisplatin sensitivity in ovarian cancer parental cells and IGF2BP1 overexpression impaired cisplatin sensitivity of parental cells. MCF2L-AS1 activated IGF2/MEK/ERK pathway through interacting with IGF2BP1. Transcription factor SP1 activated MCF2L-AS1 expression. MCF2L-AS1 knockdown inhibited ovarian cancer cisplatin-resistance in vivo. SP1-induced MCF2L-AS1 promoted ovarian cancer cisplatin-resistance through activation of IGF2/MEK/ERK pathway via interacting with IGF2BP1.

CTLA‐4 polymorphism contributes to the genetic susceptibility of epithelial ovarian cancer

AbstractAimCytotoxic T‐lymphocyte antigen‐4 (CTLA‐4), an inhibitory molecule on T‐cells, plays a key role in tumorigenesis and progression. In the present study, we investigated the effects of three polymorphisms in the CTLA‐4 gene on the risk of epithelial ovarian cancer and the clinical outcomes of patients.MethodsA case–control study was performed in 527 epithelial ovarian cancer patients and 532 controls. Genotypes of three polymorphisms were determined by polymerase chain reaction/ligase detection reaction. A survival analysis was performed in 346 patients who were followed up for more than 3 years and 208 patients who were followed up for more than 5 years.ResultsThere were significant differences in the genotype and allele distribution frequencies of the rs5742909 C/T polymorphism in CTLA‐4 between patients and controls (p = 0.009 and p = 0.04, respectively). Compared with the CC genotype, the CT + TT genotype may significantly decrease the risk of developing epithelial ovarian cancer (OR = 0.69, 95% CI = 0.52–0.91). However, no significant association between the rs231775 G/A and rs3087243 G/A polymorphisms and epithelial ovarian cancer risk was observed. The survival analysis showed that three polymorphisms may not be related to the clinical outcomes of patients.ConclusionOur results suggested that the rs5742909 C/T polymorphism of CTLA‐4 may decrease the genetic susceptibility to epithelial ovarian cancer among northern Chinese women.

Expression of Dickkopf-1 and Twist2 in Cervical Squamous Cell Carcinoma and Their Correlation with Vasculogenic Mimicry

Wnt/β-catenin signaling, epithelial-mesenchymal transition (EMT), and vasculogenic mimicry (VM) all exert important effects in tumors. Dickkopf-1 (DKK1) is an antagonist of the Wnt/β-catenin, Twist homolog 2 (Twist2) is a key EMT transcription factor involved in cancer cell migration and invasion, and VM participates in the progression and metastasis of a variety of cancers. However, the correlation of DKK1, Twist2, and VM in cervical squamous cell carcinoma(CSC) is still unclear. This study focuses on correlations among these factors as well as their correlation with clinicopathologic data and survival in CSC. DKK1, Twist2, and VM expressions were immunohistochemically examined in 116 CSC tissues and 37 normal cervical tissues. Furthermore, clinical data were processed. The expression levels of these three factors differed between CSC and normal tissues. VM was observed in CSC, but not in normal cervical tissues. Twist2 expression was high in CSC but low in normal cervical tissues, whereas DKK1 expression had the opposite pattern. Tumor cells with VM had a high expression of Twist2 and low expression of DKK1. In addition, DKK1 expression was negatively correlated with Twist2 expression. Analyzing the relationships of DKK1, Twist2, and VM with the data of patients with CSC revealed that DKK1 expression was negatively correlated with the clinical stage, degree of differentiation, depth of infiltration, and lymph node metastasis of tumors. VM and Twist2 expression were positively correlated with the degree of differentiation, the depth of infiltration, and lymph node metastasis. The positive rate of VM was greater in stage II than in stage I. The patients who expressed VM and Twist2 had a reduced overall survival (OS) when compared with patients not expressing these proteins. However, the patients who expressed DKK1 had an increased OS when compared with patients who did not show any DKK1 expression. Multivariate analysis indicated that the expressions of DKK1, Twist2, and VM were prognostic factors for CSC. VM and the expression of DKK1 and Twist2 can be the potential prognostic biomarkers and therapeutic targets for CSC.