Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, China.
Department of Biochemistry, School of Life Sciences, Nanjing Normal University, Nanjing, 210023, China.
Sci Rep. 2023 Feb 16;13(1):2775. doi: 10.1038/s41598-023-29936-8.
Oral squamous cell carcinoma (OSCC) in the context of oral submucous fibrosis (OSF) has a high incidence owing to undefined pathogenesis. Identifying key genes and exploring the underlying molecular mechanisms involved in the conversion of OSF into OSCC are in urgent need. Differentially expressed genes (DEGs) between OSCC and OSF were dug from GEO databases and a total of 170 DEGs were acquired. Functional association of DEGs were analyzed by GO and KEGG. Protein-protein interactions (PPIs) analysis was carried out and candidate biomarkers were identified by Gene co-expression analysis and Cox analyses. Hub genes were confirmed by qRT-PCR in tissues and cell lines, of which we found that IRF4 mRNA was successively up-regulated from Normal to OSF and then to OSCC and associated with immune infiltrating levels. In addition, Immunohistochemical (IHC) and Immunofluorescence (IF) assays were conducted to validate the consistent upregulation of IRF4 and the oncogene role of IRF4 in OSF and OSCC at translation level. IRF4 may be indicative biomarker in transformation of OSF into OSCC. High IRF4 expression contribute to increased immune infiltration of OSCC and may provide a novel diagnostic marker for OSCC patients translated from OSF.
口腔黏膜下纤维性变（OSF）背景下的口腔鳞状细胞癌（OSCC）由于发病机制不明确，发病率较高。因此，明确关键基因并探讨 OSF 向 OSCC 转化的潜在分子机制迫在眉睫。从 GEO 数据库中挖掘 OSCC 和 OSF 之间的差异表达基因（DEGs），共获得 170 个 DEGs。通过 GO 和 KEGG 分析 DEGs 的功能关联。通过基因共表达分析和 Cox 分析进行蛋白质-蛋白质相互作用（PPI）分析，鉴定候选生物标志物。通过 qRT-PCR 在组织和细胞系中验证关键基因，发现 IRF4 mRNA 从正常到 OSF 再到 OSCC 呈连续上调，并与免疫浸润水平相关。此外，通过免疫组织化学（IHC）和免疫荧光（IF）检测验证了 IRF4 的一致性上调以及其在 OSF 和 OSCC 中的致癌基因作用。IRF4 可能是 OSF 向 OSCC 转化的指示性生物标志物。IRF4 的高表达导致 OSCC 中免疫浸润增加，可能为 OSF 转化而来的 OSCC 患者提供新的诊断标志物。
