The Potential microRNA Prognostic Signature in HNSCCs: A Systematic Review

Abstract

Head and neck squamous cell carcinomas (HNSCCs) are often diagnosed at advanced stages, incurring significant high mortality and morbidity. Several microRNAs (miRs) have been identified as pivotal players in the onset and advancement of HNSCCs, operating as either oncogenes or tumor suppressors. Distinctive miR patterns identified in tumor samples, as well as in serum, plasma, or saliva, from patients have significant clinical potential for use in the diagnosis and prognosis of HNSCCs and as potential therapeutic targets. The aim of this study was to identify previous systematic reviews with meta-analysis data and clinical trials that showed the most promising miRs in HNSCCs, enclosing them into a biomolecular signature to test the prognostic value on a cohort of HNSCC patients according to The Cancer Genome Atlas (TCGA). Three electronic databases (PubMed, Scopus, and Science Direct) and one registry (the Cochrane Library) were investigated, and a combination of keywords such as “signature microRNA OR miR” AND “HNSCC OR LSCC OR OSCC OR oral cancer” were searched. In total, 15 systematic literature reviews and 76 prognostic clinical reports were identified for the study design and inclusion process. All survival index data were extracted, and the three miRs (miR-21, miR-155, and miR-375) most investigated and presenting the largest number of patients included in the studies were selected in a molecular biosignature. The difference between high and low tissue expression levels of miR-21, miR-155, and miR-375 for OS had an HR = 1.28, with 95% CI: [0.95, 1.72]. In conclusion, the current evidence suggests that miRNAs have potential prognostic value to serve as screening tools for clinical practice in HNSCC follow-up and treatment. Further large-scale cohort studies focusing on these miRNAs are recommended to verify the clinical utility of these markers individually and/or in combination.

Identification of Stage-Specific microRNAs That Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Genetics and Epigenetics

“…MiRNAs, a class of crucial epigenetic regulators of gene expression, have emerged as key players in precision oncology, serving as ideal biomarkers for liquid biopsy, since they exhibit strong diagnostic potential by reflecting a tissue's malignant state through the quantification of their expressional dysregulation [3,8,9,12,16]. In recent years, the expression of numerous miRNAs has been studied in OSCC, resulting in a vast number of experimental data with at least 256 molecules reported to be either upregulated or downregulated in OSCC derived-samples (tissue, saliva or blood) [6,8,9,[17][18][19][20][21][22][23][24][25][26][27][28], while the majority exhibits similar dysregulation in other neoplasms as well. Consequently, there is a state of disarray regarding the interpretation of findings and the identification of the most representative molecules for the disease at large, but particularly for its early asymptomatic stages [8].…”