Unveiling Potential Targeted Therapeutic Opportunities for Co-Overexpressed Targeting Protein for Xklp2 and Aurora-A Kinase in Lung Adenocarcinoma.

Abstract

Lung adenocarcinoma (LUAD) is one of the most prevalent and leading causes of cancer deaths globally, with limited diagnostic and clinically significant therapeutic targets. Identifying the genes and processes involved in developing and progressing LUAD is crucial for developing effective targeted therapeutics and improving patient outcomes. Therefore, the study aimed to explore the RNA sequencing data of LUAD from The Cancer Genome Atlas (TCGA) and gene expression profile datasets involving GSE10072, GSE31210, and GSE32863 from the Gene Expression Omnibus (GEO) databases. The differential gene expression and the downstream analysis determined clinically significant biomarkers using a network-based approach. These therapeutic targets predominantly enriched the dysregulation of mitotic cell cycle regulation and revealed the co-overexpression of Aurora-A Kinase (AURKA) and Targeting Protein for Xklp2 (TPX2) with high survival risk in LUAD patients. The hydrophobic residues of the AURKA-TPX2 interaction were considered as the target site to block the autophosphorylation of AURKA during the mitotic cell cycle. The tyrosine kinase inhibitor (TKI) dacomitinib demonstrated the strong binding potential to hinder TPX2, shielding the AURKA destabilization. This in silico study lays the foundation for repurposing targeted therapeutic options to impede the Protein-Protein Interactions (PPIs) in LUAD progression and aid in future translational investigations.