Implication of microRNA-regulated PTEN expression in the clinico-pathology & survival outcomes in advanced ovarian cancer
Background & objectives
Phosphatase and TENs in homolog (PTEN), deleted on chromosome 10, plays a salient role in suppressing the proliferative phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signal in cancers. Growing evidence suggests that PTEN is downregulated by microRNAs (miRs) in aggressive cancers, which antagonise its tumour-suppressive activity. This study elucidates the effect of miR-214, miR-433, miR-100, and miR-152 on PTEN expression with important clinical parameters in individuals with Stage III-IV ovarian cancer (OC).
Methods
This prospective observational study enrolled 104 individuals with OC from January 2018 to December 2020. Demographic and clinical data were collected at presentation and follow up. Tissue samples were analysed using immunohistochemistry, Western blot, and quantitative real time PCR (qPCR)s. Statistical analyses included t-tests, chi-square, correlation coefficient, log-rank, Cox regression, and ROC analysis to assess clinical and survival outcomes.
Results
The included study participants with OC (mean age 49.29±9.68 yr) presented with advanced stages (96.6%) and had high-grade serous histological subtype (48.5%). Loss of PTEN expression was detected among 50.96 per cent, indicative of poor survival (HR>1; P=<0.05). MiR-214 (P=<0.001) and miR-433 (P=<0.001) were negatively associated, while miR-100 (P<0.001) and miR-152 (P=<0.001) were positively correlated with PTEN mRNA and protein, with miR-214, and miR-152 being independent risk factors to survival of OC patients (HR=>1). The sensitivity and specificity of PTEN and miRs range between 62.5-97 per cent, with diagnostic accuracy (P=<0.001).
Interpretation & conclusions
The degree of miR-214, miR-433, miR-100, and miR-152 exhibited dysregulation in OC (P=<0.001). The findings of this study suggest that miR-214 and miR-433 can downregulate PTEN whereas miR-100 and miR-152 may have a tumour suppressive role like PTEN. Thus, the signature miR network has the potential to become a diagnostic and prognostic biomarker.