Role of MicroRNAs as diagnostic and prognostic molecular signatures in Human head and neck squamous cell carcinoma

Abstract

MicroRNAs (miR) showed thatthey had the ability to be used as prognostic markers in different cancers. There is an increasing growth in the number of the systematic review and meta-analysis on the prognostic value different miRs in various cancers in the recent years. In this study we systematically reviewed the articles investigating the prognostic value of different miRs in Human head and neck squamous cell carcinoma (HNSCC). Methods: Using on line databases (e.g. MEDLINE, Cochrane and Scopus) we identified studies that examined associations between miRs and HNSCC prognosis using either polymerase chain reaction or hybridized oligonucleotide microarrays to perform miR assay. In this study we considered clinical end points such as overall survival and disease specific survival (i.e. death and/or disease recurrence) as acceptable clinical outcome. The prognostic value is demonstrated using hazard ratio with 95% CI and if the value wasnEt reported we extracted it from Kaplan-Meier graph. Results: 20 studies pertaining to 16 different miRs were eligible for inclusion in this review. The median study size was 60.5000 (95% CI 46.3392 to 102.1519), Increased expression of miR-21, miR-210, miR-18a, miR-134a, and miR-155 associated with worsened prognosis. Lowered expression of miR-153, miR-200c, miR-363, miR-203, miR-17, miR-205, miR-Let-7d, miR-34a, miR-18a, miR-126, miR-375, miR, miR-491-p5, and miR-125b were predictor of poor prognosis. Alteration in miR-193b expression level does not show any significant association with cancer survival. While lowered expression if miR- 20a in cancerous tissue results in worsen prognosis, increased plasma level of miR-20a associates with lower survival. We performed meta-analysis on the articles choosing miR-21 as a prognostic marker. In studies included in meta-analysis different types of cut-off were used. Overall survival was used as follow-up end point in all of them. 2 studies reported adjusted OS. Totally 439 subjects was participated in this meta-analysis. A random model was applied to calculate a pooled HR and its 95% CI. We found that higher expression levels of miR-21 didnEt relate with poor survival. (Pooled HR = 1.39 - 95% CI: 0.97E2.00, P> 0.05). After omitting the study causing heterogeneity, a fixed model was applied (n=335). This time the result showed association between increased expression of miR-21 and poor survival (Pooled HR = 1.57 - 95% CI: 1.22E2.02, P < 0.05). Conclusions: Our data have shown that miR-21 may be a promising marker for prognosis prediction in HNSCC. Also other miRs are potential prognostic markers but more studies with proper methodology, sufficient samples size and follow-up duration is needed to be done to decide on the clinical efficacy of these miRs (including mir-21) as prognostic makers