The Prognostic Role of miR-31 in Head and Neck Squamous Cell Carcinoma: Systematic Review and Meta-Analysis with Trial Sequential Analysis

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with high recurrence, metastasis, and poor treatment outcome. Prognostic survival biomarkers can be a valid tool for assessing a patient’s life expectancy and directing therapy toward specific targets. Recent studies have reported microRNA (miR) might play a critical role in regulating different types of cancer. The main miR used as a diagnostic and prognostic biomarker and reported in the scientific literature for HNSCC is miR-21. Other miRs have been investigated to a lesser extent (miR-99a, miR-99b, miR-100, miR-143, miR-155, miR-7, miR-424, miR-183), but among these, the one that has attracted major interest is the miR-31. Methods: The systematic review was conducted following the PRISMA guidelines using electronic databases, such as PubMed, Scopus, and the Cochrane Central Register of Controlled Trials, with the use of combinations of keywords, such as miR-31 AND HNSCC, microRNA AND HNSCC, and miR-31. The meta-analysis was performed using the RevMan 5.41 software (Cochrane Collaboration, Copenhagen, Denmark). Results: This search produced 721 records, which, after the elimination of duplicates and the application of the inclusion and exclusion criteria, led to 4 articles. The meta-analysis was conducted by applying fixed-effects models, given the low rate of heterogeneity (I2 = 40%). The results of the meta-analysis report an aggregate hazard ratio (HR) for the overall survival (OS), between the highest and lowest miR-31 expression, of 1.59, with the relative intervals of confidence (1.22 2.07). Heterogeneity was evaluated through Chi2 = 5.04 df = 3 (p = 0.17) and the Higgins index I2 = 40; testing for the overall effect was Z = 3.44 (p = 0.00006). The forest plot shows us a worsening HR value of OS, in relation to the elevated expression of miR-31. Conclusions: In conclusion, the data resulting from the current meta-analysis suggest that miR-31 is associated with the prognosis of patients with HNSCC and that elevated miR-31 expression could predict a poor prognosis in patients with this type of neoplasm.