Identification and Evaluation of Survival-associated Common Chemoresistant Genes in Cancer

Abstract

Background: Chemoresistance is a major challenge in the effective treatment of cancer patients. This study aimed to identify common chemoresistance-associated genes that impact cancer survival. Methods: RNA-sequencing datasets for colorectal cancer (CRC) and ovarian cancer (OC) were analyzed using the gene expression omnibus (GEO) database and R Studio. Survival analysis was conducted using patient data from the cBioPortal database, where patients were stratified into high- and low-risk groups based on gene expression levels. Molecular dynamics simulations were performed to compare the binding energies of inhibitors targeting the identified genes. Results: Six common chemoresistance-associated genes were identified in both CRC and OC: cyclin-dependent kinase 2 (CDK2), inhibitor of differentiation (ID1), DUSP6, c-JUN, PLA2G2A, and SKP2. The expression of these genes was also evaluated in chemosensitive and chemoresistant oral cancer samples. Survival analysis revealed that high expression of CDK2 and ID1 significantly reduced the disease-free survival (DFS) of CRC and oral cancer patients with Grade II, III, or IV tumors. Conversely, low expression of ID1 was associated with reduced DFS in OC patients. Molecular simulations showed that the inhibitors dinaciclib (for CDK2) and vinblastine (for ID1) had higher binding energies compared to other inhibitors. Conclusion: The present study highlights the significance of CDK2 and ID1 as important mediators of chemoresistance and their potential as therapeutic targets to improve the survival of cancer patients exhibiting drug resistance.