A Systematic Review of Circulating miRNAs Validated by Multiple Independent Studies in Laryngeal Cancer

Background and Objectives: Laryngeal squamous cell carcinoma (LSCC) is a common head and neck cancer with significant morbidity and mortality. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for cancer diagnosis and prognosis. This systematic review aims to identify circulating miRNAs associated with LSCC, emphasizing those validated by at least two independent studies to improve reliability and clinical applicability. Methods: An extensive literature search was performed in the PubMed, Scopus, and Web of Science databases up to October 2024, using keywords related to LSCC and circulating miRNAs. Studies involving human participants that provided quantitative data on circulating miRNA expression levels and their clinical correlations were included. Data extraction and quality assessment were conducted following standardized protocols, highlighting miRNAs reported in multiple studies. Results: Nine high-quality studies encompassing 660 patients with LSCC and 212 controls were included. Several miRNAs were consistently identified across these studies. miR-21-5p was upregulated in four studies and associated with advanced disease stages, lymph node metastasis, and decreased survival rates. miR-125b-5p and miR-126-3p were consistently downregulated, linked to advanced clinical stages and poor tumor differentiation. miR-27a-3p was upregulated in two studies and correlated with poor prognosis, promoting LSCC progression by targeting Smad4. Additionally, miR-33a-5p was identified as a potential diagnostic biomarker with high sensitivity and specificity. These miRNAs show potential as non-invasive biomarkers for the diagnosis and prognosis of LSCC. Conclusions: This systematic review highlights specific circulating miRNAs-particularly miR-21-5p, miR-125b-5p, miR-126-3p, miR-27a-3p, and miR-33a-5p-as promising biomarkers for LSCC. The consistent findings across independent studies emphasize their potential clinical utility in early detection, prognostic assessment, and therapeutic targeting. However, further validation in larger and more diverse populations, along with the standardization of detection methods, is necessary before these biomarkers can be implemented in clinical practice.