Decoding and targeting genes regulating the malignant potential of oral proliferative leukoplakia through a sequential computational approach

Introduction

Oral proliferative leukoplakia (OPL) is a multifocal aggressive form of oral potentially malignant disorders (OPMD), carrying a higher malignant potential than solitary oral leukoplakia (OL).

Materials and Methods

The present study used a sequential computational approach to compare the molecular profile of OPL and OL to decode the genes responsible for augmenting the malignant potential of OPL. The analysis included integrated gene expression profiling, protein interaction network, molecular interconnectivity, survival assessment, and molecular docking with the existing anti-cancer drugs.

Results

OPL showed 159 genes that were distinctly upregulated compared to OL. Among these 13 genes were found to be associated with oral squamous carcinoma (OSCC). Further construction of a protein network from the 13 gene-encoded proteins activated diverse cancer-related pathways. Simultaneously, the expression of these 13 genes altered the survival rate in OSCC patients. Screening of 241 anti-cancer drugs against these 13 regulators, revealed the 3 most effective inhibitors.

Conclusion

The study decoded the key regulatory genes responsible for augmenting the malignant potential of OPL. Further, a significant association was observed between the decoded genes and the survival of OSCC patients. Anti-cancer medications capable of inhibiting these key regulators were identified. The application of the 3 most effective inhibitors could potentially prevent the malignant transformation of OPL.