Researchers have recently unveiled novel genes involved in the epithelial-to-mesenchymal transition (EMT) linked to the malignant transformation of oral submucous fibrosis (OSF), shedding light on potential new therapeutic targets for this progressive condition.
Oral submucous fibrosis, characterized as a chronic and fibrotic condition, carries with it a concerning risk of developing oral squamous cell carcinoma, with malignant transformation rates ranging from 7 to 13%. The disease is commonly associated with the consumption of areca nut, leading researchers to investigate the underlying genetic mechanisms contributing to this progression.
Through advanced genetic analysis, researchers aimed to identify and validate candidate genes regulating EMT, focusing particularly on three novel candidates: matrix metalloproteinase 9 (MMP9), secreted protein acidic and rich in cysteine (SPARC), and integrin alpha-5 (ITGA5). These genes were identified using differential gene expression analysis based on data retrieved from the Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) pertinent to head and neck squamous cell carcinomas.
The study revealed distinctive patterns of gene expression, finding MMP9 significantly upregulated in oral cancer samples compared to normal tissues. SPARC and ITGA5 were similarly found to be more prevalent, reinforcing their potential roles in fostering tumorigenesis. The researchers observed these proteins predominantly localizing within the cytoplasmic compartment of neoplastic cells, highlighting their involvement at both the transcriptional and translational levels within OSF and OSCC samples.
“The significant roles of MMP9, SPARC, and ITGA5 in fibrosis and malignancy suggest a novel mechanism where fibrosis-associated type 2 EMT transitions to type 3 EMT, driving OSF toward malignancy,” stated the authors of the article, emphasizing the clinical urgency of their findings.
To validate the results, comprehensive pathway analysis and immunohistochemical investigations were employed, confirming associations between the curated gene expressions and several cancer states such as angiogenesis and metastasis. The findings collectively indicate the involvement of these genes as potential targets to prevent or halt the malignant transformation of OSF.
With oral cancer being one of the more significant global health concerns, reported to have contributed to approximately 377,713 new cases worldwide just last year, these findings bolstering our comprehension of the molecular underpinnings of OSF offer hopeful avenues for targeted therapy development.
To this end, researchers advocate pursuing pharmacological strategies aimed at inhibiting the activities of MMP9, SPARC, and ITGA5 to curb the progression of fibrosis and malignant transformation pathways. The study underlines the complex interplay of gene regulation involving fibrosis and malignancy, echoing the need for continued investigations and enhanced therapeutic focus toward these candidate genes.