Comparative functional and molecular analysis of oral submucous fibrosis to oral squamous cell carcinoma: A pathway-based dynamic network analysis

Abstract

Abstract OSF (Oral submucous fibrosis) has been categorized as an OPMD (oral pre-malignant disease). It is frequently associated with areca chewing, a prevalent habit in Southeast Asia. The OSF is one of the leading causes of oral cancer and OSF and high prevalence of OSF-associated oral cancer is recorded in South India and Southeast Asia. The molecular mechanism of the transformation of OSF into OSCC is not properly understood. Identifying key genes and exploring the underlying molecular mechanisms involved in the transformation of OSF into OSCC is therefore of great importance. It may lead to the identification of new diagnostics, and ways to prevent the development of oral cancer from OSF. Therefore, in the present study, we devised a bioinformatics pipeline using gene expression analysis, dynamic protein-protein interaction network, and functional enrichment analysis to understand the transformation of OSF into oral cancer. We identified gene expressions in different stages of transformation i.e. OSF without dysplasia (OSFWT), OSF with dysplasia (OSFWD), and further Oral squamous cell carcinoma (OSCC). OSF-associated 52 dysplastic genes were identified that were found to enrich the assembly of collagen fibrils and other multimeric structures, wound healing, spreading of cells, and sodium ion transmembrane transport processes. Important dysplastic genes such as COL1A2, COL5A1, COL5A2, COL6A1, DLG4, CS, and ALDH5A1 were proposed. Important dynamic (Dy) nodes were identified using enriched pathways. MYC is identified as the most important node in OSF with a high Dn-score. Dy-nodes were mostly enriched in immune system pathways suggesting immune involvement in OSCC progression. A few important genes were identified based on their frequency in every observation such as HSPD1, MAPT, HNRNPK, TRIM24, HLA-C, FOS, CD79B, TMPO, and PTPN6. In conclusion, our study identified a group of potential genes involved in OSF and OSF transformation into oral cancer and their functions.