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Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis
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Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis
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Journal Article
Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis
2025
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 692/4028
/ Cancer
/ Carcinoma, Squamous Cell - genetics
/ Carcinoma, Squamous Cell - pathology
/ Cell Transformation, Neoplastic - genetics
/ Cell Transformation, Neoplastic - pathology
/ Computational Biology - methods
/ EMT
/ Epithelial-Mesenchymal Transition - genetics
/ Fibrosis
/ Gene Expression Regulation, Neoplastic
/ Humanities and Social Sciences
/ Humans
/ Matrix Metalloproteinase 9 - genetics
/ Matrix Metalloproteinase 9 - metabolism
/ Mouth Neoplasms - metabolism
/ Oral squamous cell carcinoma
/ Oral Submucous Fibrosis - genetics
/ Oral Submucous Fibrosis - metabolism
/ Oral Submucous Fibrosis - pathology
/ Science
