Integrative analysis of PTEN‐related hub genes and validating drug targets for colorectal cancer

Abstract

Colorectal cancer (CRC) is a heterogeneous disease and one of the most prevalent malignancies worldwide. Previous research has indicated that phosphatase and tensin homolog (PTEN)‐related genes found in CRC may serve as potential biomarkers for individualized treatment options. The present study aimed to examine the association between PTEN‐related genes and the prognosis of CRC patients by evaluating the significance of PTEN‐related hub genes and determining potential mechanisms and genes associated with them. Gene expression profiles and clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. At present, PTEN mutations have been identified in 7% of CRC patients, according to the most recent TCGA data. Differential expression analysis revealed 54 genes as differentially expressed genes (DEGs) between PTEN‐related genes and GEO databases (GSE39582 and GSE6263). Further gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted on PTEN‐related DEGs. The prognostic efficacy of the PTEN‐related DEG signature was assessed using Kaplan–Meier survival and receiver operating characteristic curve analyses. Bioinformatics methods were utilized to analyze the correlation between PTEN‐related DEGs and CRC prognosis, survival, and drug efficacy. Through these analyses, eight prognostic‐related PTEN‐related hub genes (PPARGC1A, NTRK2, ANK2, PLCB4, STC2, PLAU, CDKN1A, and HPGDS) were identified and a risk prognosis model was constructed. Notably, NTRK2 and HPGDS were found to affect drug treatment response in CRC. Targeting these prognostic‐related PTEN‐related hub genes can regulate cell death signaling, which may benefit the prognosis of CRC patients and improve drug sensitivity.