Shetty Smitha Sammith, Ram Padam Kanaka Sai, Sharma Mohit, Kudva Adarsh, Patel Pratik, Radhakrishnan Raghu
Department of Oral and Maxillofacial Pathology and Microbiology, Manipal College of Dental Sciences, Manipal Academy of Higher Education, Manipal, 576104, India.
Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Sci Rep. 2025 Jan 26;15(1):3294. doi: 10.1038/s41598-025-87790-2.
Oral submucous fibrosis (OSF) is a chronic, progressive, and fibrotic condition of the oral mucosa that carries an elevated risk of malignant transformation. We aimed to identify and validate novel genes associated with the regulation of epithelial-to-mesenchymal transition (EMT) in OSF. Genes regulating EMT were identified through differential gene expression analysis, using a LogFC threshold of -1 and + 1 and a padj value < 0.05, based on data from GEO datasets and the TCGA-HNSC datasets. The curated EMT genes were correlated with functional cancer states and subjected to clustering to identify candidate genes. Integration of bioinformatics and proteomics led to the discovery of the EMT genes MMP9, SPARC, and ITGA5 as novel candidates. Comprehensive pathway and immunohistochemical analyses confirmed their roles in regulating EMT in OSF, oral squamous cell carcinoma (OSCC), and OSF-associated squamous cell carcinoma (OSFSCC). The significant roles of MMP9, SPARC, and ITGA5 in fibrosis and malignancy suggest a novel mechanism in which fibrosis-associated type 2 EMT undergoes transition to type 3 EMT, driving OSF towards malignancy.
口腔黏膜下纤维化（OSF）是一种口腔黏膜的慢性、进行性纤维化疾病，具有较高的恶变风险。我们旨在识别并验证与OSF中上皮-间质转化（EMT）调控相关的新基因。基于来自GEO数据集和TCGA-HNSC数据集的数据，通过差异基因表达分析，使用LogFC阈值-1和+1以及padj值<0.05来识别调控EMT的基因。对整理后的EMT基因与功能性癌症状态进行关联，并进行聚类以识别候选基因。生物信息学和蛋白质组学的整合导致发现EMT基因MMP9、SPARC和ITGA5为新的候选基因。全面的通路和免疫组织化学分析证实了它们在调控OSF、口腔鳞状细胞癌（OSCC）和OSF相关鳞状细胞癌（OSFSCC）中的EMT作用。MMP9、SPARC和ITGA5在纤维化和恶性肿瘤中的重要作用提示了一种新机制，即纤维化相关的2型EMT转变为3型EMT，促使OSF恶变。
