Systematic Review: Genetic and epigenetic Changes involved in the Progression of Oral Squamous Cell Carcinoma

Abstract

Introduction: Oral squamous cell carcinoma (OSCC) remains one of the most prevalent malignancies worldwide, particularly in regions with high tobacco and areca nut consumption. Its pathogenesis is a multistep process influenced by both genetic predispositions and epigenetic modifications. Recent advances have identified key molecular alterations including DNA methylation, non-coding RNAs, and genetic polymorphisms that may serve as potential biomarkers for diagnosis, prognosis, and therapeutic targeting.

Objectives: This systematic review aims to comprehensively evaluate the genetic and epigenetic changes implicated in OSCC progression.

Materials and Methods: This review adhered to PRISMA guidelines. A systematic literature search was conducted in PubMed and Scopus databases, retrieving 625 and 321 articles respectively. After screening titles, abstracts, and full texts based on predefined inclusion criteria, 10 studies were included for qualitative synthesis. Data were extracted regarding study size, molecular markers evaluated, techniques employed, and key findings. Both observational and experimental studies involving OSCC tissues, cell lines, or clinical samples were considered.

Results: Among the 11 included studies, a diverse range of epigenetic and genetic markers were investigated. Notable findings include MIR146A polymorphism linked to OSCC susceptibility, promoter hypermethylation of tumor suppressor genes such as P15, P16, TP53, and VHL, and aberrant expression of miRNAs like miR-99b-3p, miR-100-5p, and miR-148a. Long non-coding RNAs (LINC00974) and circular RNAs (circ_0072387) were shown to modulate OSCC progression via interactions with miR-122 and miR-503-5p respectively. Epigenetic studies were more predominant compared to genetic analyses, reflecting a relative paucity of studies addressing genetic alterations. Most studies used PCR-based techniques, with tissue samples as the primary source.

Conclusion: This review underscores the significant role of both genetic and epigenetic mechanisms in the pathogenesis and progression of OSCC. Epigenetic markers, particularly miRNAs and DNA methylation changes, are consistently reported as potential diagnostic and prognostic tools. However, a noticeable gap exists in the literature regarding genetic studies in OSCC, indicating the need for more comprehensive investigations. Future research should focus on large-scale, multi-omics approaches and non-invasive biomarker discovery to facilitate early detection and improve patient outcomes.