Variation of Gene Expression and Methylation Profiling in Gingival and Tongue Cancers

ABSTRACT While the development of innovative drugs has improved the outcomes of various cancers in recent years, the number of patients with oral squamous cell carcinoma (OSCC) and mortality rates has not yet decreased significantly. This could be attributed to the prognostic and molecular differences occurring at different locations of cancer development. In this study, we conducted gene expression, DNA methylation, and tumor immunological analyses of gingival squamous cell carcinoma (GSCC) and tongue squamous cell carcinoma (TSCC) to elucidate the characteristic gene expression changes, their mechanisms, and tumor immune profiles. Gene expression analysis suggested that pathways related to the cell cycle and antibacterial humoral immunity were upregulated in GSCC, whereas immune response pathways were upregulated in TSCC. Additionally, high HOXC13 expression may be associated with GSCC prognosis. DNA methylation analysis revealed hypermethylation of the 3′ UTR of the HOXD11 gene, leading to increased expression in both GSCC and TSCC. In the tumor immune profile analysis, when comparing tumor and normal tissues in GSCC, the number of immune cells did not change significantly; however, the proportion of inflammatory cells, such as CD8+ T cells, changed. In TSCC, the number and percentage of inflammatory cells, such as T lymphocytes, increased in the tumor compared to those of normal tissues. These findings underscore the importance of understanding the characteristics of site‐specific OSCC. Therefore, it is essential to establish standardized treatment protocols and develop novel therapeutic strategies tailored to each anatomical site of the tumor.