A p۵۳ Pathway-Based Eight-Gene Prognostic Signature for Risk Stratification and Survival Prediction in Colorectal Cancer: A TCGA-COAD Transcriptomic Analysis

Background: Colorectal cancer (CRC) remains a major global health challenge, ranking among the leading causes of cancer incidence and mortality despite continuous advances in diagnosis and treatment. Because alterations in the TP۵۳ signaling pathway play a central role in colorectal tumorigenesis by regulating genomic stability, apoptosis, and cell-cycle control, genes involved in this pathway may serve as valuable prognostic indicators. This study aimed to establish a TP۵۳ pathway-derived gene signature for predicting survival outcomes in patients with colorectal cancer. Methods: Transcriptomic profiles together with corresponding clinical information from ۴۶۱ patients with primary colon adenocarcinoma in the TCGA-COAD cohort were analyzed. After filtering and TMM normalization of RNA-sequencing data, ۲۰۰ TP۵۳ pathway genes obtained from the MSigDB Hallmark collection were screened using univariate Cox proportional hazards analysis. Eight prognostically relevant genes (VWA۵A, SLC۳۵D۱, KLF۴, RGS۱۶, INHBB, FUCA۱, KIF۱۳B, and CDKN۲A) were integrated into a risk-scoring model. Patients were subsequently categorized into low- and high-risk groups according to the median risk score. Model performance was evaluated using Kaplan–Meier survival analysis, Cox regression, time-dependent ROC analysis, and differential gene-expression testing. Results: Patients assigned to the high-risk group experienced significantly shorter overall survival than those in the low-risk group (log-rank p < ۰.۰۰۱). The calculated risk score remained significantly associated with survival outcome (HR > ۱, p < ۰.۰۰۱), indicating its prognostic relevance. Predictive accuracy was supported by ۱۲-month AUC values ranging from ۰.۷۵ to ۰.۸۵. Moreover, all eight genes displayed significant expression differences between the two risk groups, with KLF۴ and FUCA۱ exhibiting the strongest differential expression. Conclusions: The proposed TP۵۳ pathway-based eight-gene model effectively stratifies colorectal cancer patients according to survival risk and represents a promising transcriptomic biomarker for prognostic assessment. Nevertheless, independent external validation and experimental investigations are required before its potential clinical application can be fully established.

کلیدواژه ها:

Colorectal cancer ، p۵۳ pathway ، prognostic signature ، risk stratification ، TCGA-COAD