Altered miRNA Profiles in Oral Squamous Cell Carcinoma Patients Relative to Healthy Controls: A Systematic Review

Abstract

Background: Oral squamous cell carcinoma (OSCC) remains a major cause of cancer morbidity and mortality, largely due to late-stage presentation and early metastatic potential. MicroRNAs (miRNAs) regulate oncogenic and tumor suppressive pathways and have emerged as promising diagnostic and prognostic biomarkers measurable in tissue and body fluids. Objective: To systematically identify miRNAs differentially expressed in OSCC patients compared with healthy controls across tissue, plasma, and saliva specimens. Methods: A PRISMA-guided systematic review was conducted using Embase, PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar, with ProQuest used to search grey literature. Eligible studies included human OSCC case–control designs reporting differential miRNA expression between OSCC cases and healthy controls using tissue, plasma, or saliva samples. Two reviewers performed study selection and data extraction independently, with methodological quality assessed using the Newcastle–Ottawa Scale. Findings were synthesized narratively due to heterogeneity in specimen types and miRNA targets. Results: Six case–control studies were included. In saliva, hsa-miR-30c-5p was downregulated, while hsa-miR-423-5p, hsa-miR-106b-5p, and hsa-miR-193b-3p were upregulated in OSCC. In plasma, hsa-miR-31 was upregulated. In tissue, downregulation of hsa-miR-204, hsa-miR-144, and hsa-miR-375 and upregulation of hsa-miR-196a, hsa-miR-21, and hsa-miR-155 were reported. Most studies were high quality. Conclusion: OSCC is associated with reproducible miRNA dysregulation across multiple biological matrices, supporting miRNAs as candidate biomarkers; however, evidence remains limited and requires standardized validation, including diagnostic accuracy assessment and external replication