Biomarkers

Prognostic prediction of oxidative stress related hematological biomarkers in locally advanced cervical cancer patients undergoing chemoradiotherapy

This investigation aimed to develop and validate a novel oxidative stress score for prognostic prediction in locally advanced cervical cancer (LACC) patients receiving chemoradiotherapy. A total of 301 LACC patients were enrolled and randomly divided into a training and a validation set. The association between oxidative stress parameters and prognosis was analyzed for oxidative stress score (OSS) establishment. A Cox regression model was conducted for overall survival (OS) and progression-free survival (PFS). A nomogram prediction model was developed using independent prognostic factors from the training set and validated in the validation set. A novel OSS was established with four oxidative stress parameters, including albumin, total bilirubin, blood urea nitrogen, and lactate dehydrogenase. Multivariate regression analysis identified OSS as an independent prognostic factor for OS ( This study confirmed that preoperative OSS could serve as a useful independent prognostic factor in LACC patients who received CCRT.

The diagnostic value of serum YKL-40 in endometrial cancer: a meta-analysis

Serum YKL-40 is a promising non-invasive biomarker for the early diagnosis of endometrial cancer (EC), but its value is disputed. To investigate the serum YKL-40 in the early diagnostic value of EC. Databases were systematically searched again before April 2021 and 14 studies were finally included in this meta-analysis. Pooled sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve analyses were assessed. This meta-analysis investigated the source of heterogeneity using sensitivity analysis, subgroup analysis, and meta-regression. Databases were systematically searched again before April 2021 and 14 studies were finally included in this meta-analysis. First, the SROC curve presented an area under the curve (AUC) of 0.853 (SE = 0.0213) for YKL-40 alone and an AUC of 0.946 (SE = 0.0268) for YKL-40 combined with other biomarkers. Second, diagnostic types might be related to the diagnostic accuracy and is a significant source of heterogeneity ( Serum YKL-40 helped diagnose EC, and its combination with other biomarkers was better than itself alone.

Deciphering the potential of proteomic-based biomarkers in women’s reproductive diseases: empowering precision medicine in gynecology

Gynecological disorders represent a complex set of malignancies that result from a diverse array of molecular changes affecting the lives of over a million women worldwide. Ovarian, Endometrial, and Cervical cancers, Endometriosis, PCOS are the most prevalent ones that pose a grave threat to women's health. Proteomics has emerged as an invaluable tool for developing novel biomarkers, screening methods, and targeted therapeutic agents for gynecological disorders. Some of these biomarkers have been approved by the FDA, but regrettably, they have a constrained diagnostic accuracy in early-stage diagnosis as all of these biomarkers lack sensitivity and specificity. Lately, high-throughput proteomics technologies have made significant strides, allowing for identification of potential biomarkers with improved sensitivity and specificity. However, limited successes have been shown with translation of these discoveries into clinical practice. This review aims to provide a comprehensive overview of the current and potential protein biomarkers for gynecological cancers, endometriosis and PCOS, discusses recent advances and challenges, and highlights future directions for the field. We propose that proteomics holds great promise as a powerful tool to revolutionize the fight against female reproductive diseases and can ultimately improve personalized patient outcomes in women's biomedicine.

Role of biomarkers CA-125, CA-15.3 and CA-19.9 in the distinction between endometriomas and ovarian neoplasms

To evaluate the utilisation of CA-125, CA-15.3 and CA-19.9 in differentiating between ovarian neoplasms and endometriomas, and the best cut-off value for these tumour markers in this differentiation. Preoperative serum values of CA-125, CA-15.3 and CA-19.9 were evaluated in 265 patients undergoing surgery for adnexal masses, being 32 non-neoplastic lesions, 134 benign neoplasms, 19 borderline tumours, 36 malignant neoplasms, and 44 endometriomas. ROC curves and Univariate and multivariate analyses were performed. Only CA-19.9 was useful in differentiating between endometriomas and ovarian neoplasms (benign and malignant tumours), being this marker found at higher levels in endometriomas. In multivariate analyses, CA-19.9 greater than 22.3 U/mL was considered an independent factor for the diagnosis of endometrioma, comparing endometrioma and ovarian cancer. Comparing endometrioma and all other groups, the clustering analysis using the combination CA-125 > 34.28 U/mL and CA-19.9 > 19.12 U/mL demonstrated that this association was considered an independent factor for the diagnosis of endometrioma. CA-9.9 is useful in distinguishing between endometriomas and ovarian cancer, and its combination with CA-125 is useful in differentiating endometrioma from other ovarian lesions.

Upregulation of ESPL1 is associated with poor prognostic outcomes in endometrial cancer

Extra spindle pole bodies-like 1 ( The TCGA and GEO databases were utilized to assess the expression of Our analysis revealed that The upregulation of

The vasculogenic mimicry, CD146 + and CD105 + microvessel density in the prognosis of endometrioid endometrial adenocarcinoma: a single-centre immunohistochemical study

The microvessel compartment is crucial in the tumour microenvironment of endometrioid adenocarcinoma (EA). This study investigated the role of vasculogenic mimicry (VM), CD146, and CD105 microvessel density in the clinical prognosis of EA. A total of 188 EA cases were analyzed, with VM channels and microvessels detected using PAS/CD31, CD146, and CD105 staining. Mann-Whitney and Fisher exact tests were used to compare the study groups according to the evaluated criteria. ROC analysis included determination of the confidence interval (CI) and area under the ROC curve. The Mantel-Cox test was used to analyze progression-free survival. Multivariate Cox proportional hazard analysis was performed using stepwise regression. Results showed that VM channels and CD146 and CD105 microvessels were significantly higher (

Potential biomarkers in endometrial cancer: a narrative review

Every year, approximately 0.4 million women suffer from endometrial cancer (EC) worldwide and it has become the most common gynecological malignancy. Almost 66% of EC cases are diagnosed at an early stage and can be cured by performing surgery while those at an advanced stage turns out to be fatal. Biomarkers of endometrial cancer would be very valuable for screening of women who are at high risk and in detecting the chance of recurrence of disease. The current article has reviewed studies published on expression of biomarkers and susceptibility to EC. Google Scholar and PubMed were used as searching platforms and we have majorly considered the literature from last 10 years. Potential biomarkers of EC identified from various studies were summarised.

Impact of MDM2 promoter SNP55 (rs2870820) on risk of endometrial and ovarian cancer

While large GWAS analyses have not found convincing associations between Using a custom LightSNiP assay, we genotyped SNP55 in two large hospital-based cohorts of patients with ovarian (n = 1,332) and endometrial (n = 1,363) cancer and compared genotypes to healthy female controls (n = 1,858). Among individuals harbouring the SNP309TT genotype, the minor SNP55T-allele was associated with a reduced risk of endometrial (dominant model: OR = 0.63; CI = 0.45-0.88;

MiR-150 and miR-155 expression predicts survival of cervical cancer patients: a translational approach to novel prognostic biomarkers

High-risk human papillomavirus (HPV) is the aetiological agent of cervical cancer, which remains the fourth leading cause of cancer death in women worldwide. K14-HPV16 transgenic mice are a model for HPV-induced cancers, which undergo multistep squamous carcinogenesis at the skin, that is histologically and molecularly similar to carcinogenesis of the human cervix. Previous screens of differentially regulated microRNAs (miRs) using K14-HPV16 mice showed a role for miR-21, miR-155, miR-150, miR-146a, miR-125b and miR-223 during carcinogenesis. We now aim to translate these observations into the clinical setting, using data provided by The Cancer Genome Atlas (TCGA) to explore whether those microRNAs can influence the survival of cervical cancer patients. Results showed that low miR-150, miR-155 and miR-146a expression levels in primary tumours were associated with poor overall survival. However, only miR-150 and miR-155 were found to be independent predictors, increasing the risk of death. When patients were stratified by clinical stage, low miR-150, miR-155, miR-146a and miR-125b were associated with poor survival for clinical stages I and II. Only low miR-150 expression increased the death risk. We conclude that miR-150 and miR-155 may be potentially applied as prognostic biomarkers in cervical cancer patients. However, further investigation is required to determine their applicability.

Evaluating a data-driven approach to biomarker discovery for tumor-targeted imaging in epithelial ovarian cancer

Arginase is upregulated in healthy women infected by oncogenic HPV types

The implication of arginase enzyme in Human Papillomavirus (HPV) infections has not been clearly elucidated. The present study investigates whether HPV infection is correlated with changes in plasmatic arginase activity and cervical ARG1 and ARG2 mRNA expression among infected women negative for intraepithelial lesions (NIL). The present study included 300 women. The plasmatic arginase activity was evaluated by a colorimetric assay. Cervical HPV was detected by real-time PCR. The circulating viral load and ARG1 and ARG2 mRNA expression quantification were performed by quantitative real-time PCR. A significant increase in plasma arginase activity and ARG1 and ARG2 mRNA expression levels in cervical cells was observed among HPV-positive women compared to the HPV-negative group. The highest levels were significantly associated with oncogenic HPV, and increased arginase activity was associated with a high HPV circulating viral load. Moreover, the highest levels of arginase activity were observed in oncogenic HPV-positive inflammatory smears. These data suggest that HPV could modulate arginase activity and expression, which may restrict arginine bioavailability and inhibit this amino acid's antiviral properties. Our findings revealed that arginase activity and isoform gene expression were upregulated in women with HPV infection, particularly the oncogenic HPV types.

Serum cytokines and CXCR2: potential tumour markers in ovarian neoplasms

The aim was to investigate the systemic levels of cytokines and the expression of the chemokine receptor CXCR2 in circulating neutrophils in patients with non-neoplastic ovarian lesions, benign neoplasia or malignant neoplasia. Controls and patients with ovarian tumours were pre-operatively compared for the production of cytokines (IL-2, IL-5, IL-6, IL-8, IL-10 and TNF-α) by ELISA, and for the expression of the chemokine receptor, CXCR2, in neutrophils, by flow cytometry. Randomly selected patients within the malignant group were re-evaluated for the inflammatory parameters at 30 days after surgery. The serum concentrations of IL-6, IL-8 and IL-10 were significantly higher in the benign and malignant neoplasia than in the control group, and their levels were significantly higher in ovarian cancer patients than in patients with non-neoplastic tumours or benign neoplasia. Treatment reduced IL-8 serum levels but did not affect CXCR2 expression in neutrophils. Cut-off values for IL-6, IL-8, and IL-10 comparing malignant vs. benign neoplasia were 11.3, 71.7, 14.8, and comparing malignant neoplasm vs. non-neoplastic lesions were 7.2, 43.5, 12.3, respectively. Serum IL-6, IL-8, and IL-10 levels, and expression of CXCR2 in circulating neutrophils seem promising for distinguishing ovarian cancer patients from patients with benign tumours.

Monomeric myeloperoxidase is a specific biomarker for early-stage ovarian cancer