Comparative Study of key cellular polarity proteins’ expression in oral dysplasia and oral squamous cell carcinoma using a combined immunohistochemistry and transcriptomics- based approach

Objective: The process by which oral precancerous lesions turn malignant—especially through Epithelial-Mesenchymal Transition (EMT)—is closely tied to changes in certain cell polarity proteins. This groundbreaking study explores how key polarity proteins (PAR3, SCRIBBLE, and DLG7) are expressed in different tissue types: oral epithelial dysplasia (OED), oral squamous cell carcinoma (OSCC), and normal oral mucosa (NOM). The research combines histopathology, immunohistochemistry, and whole-transcriptome sequencing for a comprehensive analysis. Materials and Methods: The study examined tissue samples from 50 tobacco users in West Bengal, India. These samples, preserved in formalin and embedded in paraffin, were stained with hematoxylin and eosin to help identify and classify various stages of OED and OSCC (both well- and moderately-differentiated). Further testing used immunohistochemistry to detect PAR3, SCRIBBLE, and DLG7 proteins. Additionally, RNA sequencing was performed on samples from 25 oral cancer patients who had both OED and OSCC lesions from an independent patient cohort, to analyze differences in gene expression related to the same proteins. Findings: Using IBM SPSS version 20.0, statistical tests (Chi-square) showed that PAR3, SCRIBBLE, and DLG7 were either significantly reduced or completely missing in both OED and OSCC cases. In contrast, these proteins were moderately to strongly expressed in normal oral tissues. Conclusion: The study found a clear and consistent reduction or loss of cell polarity proteins as tissue progresses from a precancerous to a cancerous state. The immunohistochemistry results matched the RNA sequencing data, suggesting that the breakdown of cell polarity is an early and crucial step in the development of oral cancer. These proteins could serve as valuable biomarkers for identifying when oral potentially malignant disorders (OPMDs) begin turning into cancer and may play a key role in cancer initiation, progression, and spread.