NOVEL SOLUTION BASED ON DETECTION OF MIRS-410-3P AND 141-5P FOR DIAGNOSTIC OF PROSTATE CANCER EVOLUTION

Abstract

AbstractTo date, prostate cancer (PCa) is both the most common tumour diagnosed in males and the second most common cause of cancer-related mortality(1,). Prevention programs and screening protocols have proven useful to detect the disease at population level, but they lack sensitivity and specificity in comparison to the molecular tests routinely available for screening of other types of cancer, leading to unnecessary biopsies and overtreatment in many cases. In this context, a new set of small RNA biomarkers are surfacing with promising results to predict tumour progression, risk reclassification and treatment response(2)such as miR-410-3p -3p and miR-141-5p. Former studies where these biomarkers were examined in prostate cancer tissues and cell lines by qRT-PCR have shown that high expression of miR-410-3p -3p correlates to both a) accurate diagnosis in certain groups where the PSA levels do not match results from biopsy, surgery and/or digital rectal examination and b) poor prognosis of prostate cancer patients(3). Likewise, miR-141-5p shows a parallel behaviour suggesting a potential combo for fine molecular analysis of the ratios. In this sense, recent studies have demonstrated that miR-410-3p -3p exert oncogenic functions through downregulating PTEN, proving that miR-410-3p -3p inhibits prostate cancer progression via downregulating PTEN/AKT/mTOR signalling pathway. Curiously enough, different behaviour has been reported for the biomarker in both, peripheral blood from patients and cancer-cell line(s)(34.5.6)models further pointing at the advantages of a dual gauging made possible by parallel semi-quantitation of miR-141-5p. In this sense, miR-141-5p has been clearly identified as to be upregulated in large cohorts (n over 500) of prostate cancer patients confirming overexpression in multivariate analysis in tumour epithelium and tumour stroma. This overexpression taken into the context of a peripheral blood reduction of miR-410-3p appears to be associated with increased risk of biochemical cancer recurrence in an independent study over 500 patients(7). Here we present the design, molecular set up and preclinical assessment of a novel system that uses the discarded volume from PSA blood tests to predict prostate cancer progression and biochemical cancer recurrence via detection of the biomarkers. The method described could potentially eliminate the need of invasive means such as biopsy, surgery and digital rectal examination.