MicroRNAs in Salivary Gland Cancers Associated with Poor Prognosis: A Systematic Review

Salivary gland cancers (SGCs) are rare and heterogeneous tumours, making the identification of reliable prognostic biomarkers challenging. MicroRNAs (miRNAs) regulate post-transcriptional gene expression and may play important roles in tumour progression and treatment response. This systematic review aims to identify and summarize the current evidence on miRNA dysregulation in SGCs, with a particular focus on their prognostic relevance and therapeutic potential. A systematic search of PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library was conducted up to 3 December 2025, following PRISMA guidelines and a pre-registered protocol (CRD420251231827). Observational cohort and cross-sectional studies reporting microRNA dysregulation in human salivary gland tissues with prognostic assessment were included. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. Due to considerable heterogeneity, a narrative synthesis was conducted. Twenty studies published between 2013 and 2025 that fulfilled the search criteria were further analyzed. Based on the currently available evidence, dysregulation of miRNAs associated with prognosis has been identified only in adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC). Most studies originated from Asia and used qRT-PCR for miRNA assessment. Most researchers focused on the evaluation of selected candidate miRNAs, rather than conducting comprehensive miRNA profiling approaches in relation to prognosis. Several distinct dysregulated miRNAs were identified across the studies. Among them, miR-9, miR-21, miR-24 miR-29, miR-34c-5p, miR-125a-5p, miR-143, miR-145 and miR-205 were reported in more than one study and linked to clinicopathological advancement and a more aggressive disease course, thus leading to a poorer outcome. MiRNAs appear to represent promising prognostic biomarkers, either as independent predictors or in combination with established clinicopathological features. However, current evidence remains limited to selected histological subtypes and relatively small patient cohorts. Further well-designed studies with long-term follow-up are required. Moreover, comprehensive miRNA profiling with prognosis assessment is necessary before specific miRNAs could be reliably established as biomarkers and utilized in daily clinical practice.