Margaritis Avgeris

tRNA-derived small RNA 3′U-tRFValCAC promotes tumour migration and early progression in ovarian cancer

Despite recent advances in epithelial ovarian cancer (EOC) management, the highly heterogenous histological/molecular tumour background and patients' treatment response obstructs personalised prognosis and therapeutics. Herein, we have studied the role and clinical utility of the novel subclass of tRNA-derived small RNA fragments emerging via 3'-trailer processing of pre-tRNAs (3'U-tRFs) in EOC. SK-OV-3 and OVCAR-3 cells were used for in vitro study. Following transfection, cell growth and migration were assessed by CCK8 and wound healing assays, respectively. 3'U-tRFs levels were assessed by reverse transcription quantitative PCR (RT-qPCR), following 3'-end RNA polyadenylation. A screening (OVCAD, n = 100) and institutionally independent validation (TU Munich, n = 103) cohorts were employed for survival analysis using disease progression and patients' death as clinical end-points. Bootstrap analysis was performed for internal validation, and decision curve analysis was used to evaluate clinical benefit on disease prognosis. Following primary clinical assessment, target prediction and gene ontology analyses, the 3'U-tRF 3'U-tRF

miR‐181a overexpression predicts the poor treatment response and early‐progression of serous ovarian cancer patients

AbstractOvarian cancer (OC) remains a leading cause of gynecological cancer‐related death worldwide, characterized by poor 5‐year survival. Molecular markers could serve as crucial tools of personalized prognosis and therapy. Herein, we present miR‐181a as novel predictor of OC prognosis, using five independent OC cohorts. In particular, a screening (n = 81) and an institutionally independent validation (n = 100, OVCAD multicenter study) serous OC (SOC) cohorts were analyzed. Bagnoli et al (2016) OC179 (n = 124) to OC133 (n = 100) and TCGA (n = 489) served as external validation cohorts. Patients’ survival and disease progression were assessed as clinical endpoint events. Bootstrap analysis was performed for internal validation and decision curve analysis was utilized to evaluate clinical benefit. miR‐181a overexpression was unveiled as powerful and independent molecular predictor of patients’ poor survival and higher risk for disease progression after debulking surgery and platinum‐based chemotherapy. Analysis of the OVCAD institutionally independent cohort, as well as of Bagnoli et al. and TCGA external cohorts further confirmed the unfavorable prognostic nature of miR‐181a overexpression in SOC. Strikingly, multivariate prognostic models incorporating miR‐181a with established disease markers clearly improved patients’ risk‐stratification and offered superior clinical benefit in OC prognostication. Conclusively, miR‐181a evaluation could augment prognostic accuracy and support precision medicine decisions in OC.

miR-203 is an independent molecular predictor of prognosis and treatment outcome in ovarian cancer: a multi-institutional study

Abstract Ovarian cancer (OC) accounts for the most gynecological cancer-related deaths in developed countries. Unfortunately, the lack of both evident early symptoms and effective asymptomatic population screening results in late diagnosis and inevitably poor prognosis. Hence, it is urgent to identify novel molecular markers to support personalized prognosis. In the present study, we have analyzed the clinical significance of miR-203 in OC using two institutionally independent cohorts. miR-203 levels were quantified in a screening (n = 125) and a validation cohort (n = 100, OVCAD multicenter study). Survival analysis was performed using progression and death as clinical endpoint events. Internal validation was conducted by bootstrap analysis, and decision curve analysis was used to evaluate the clinical benefit. Increased miR-203 levels in OC patients were correlated with unfavorable prognosis and higher risk for disease progression, independently of FIGO stage, tumor grade, residual tumor after surgery, chemotherapy response and age. The analysis of the institutionally independent validation cohort (OVCAD study) clearly confirmed the shorter survival outcome of the patients overexpressing miR-203. Additionally, integration of miR-203 levels with the established disease prognostic markers led to a superior stratification of OC patients that can ameliorate prognosis and benefit patient clinical management. In this regard, miR-203 expression constitutes a novel independent molecular marker to improve patients’ prognosis in OC.