Human Genetics and Genomics

en A p53 Pathway-Based Eight-Gene Prognostic Signature for Risk Stratification and Survival Prediction in Colorectal Cancer: A TCGA-COAD Transcriptomic Analysis عمومى Human Genetics پژوهشي Research 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 TP53 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 TP53 pathway-derived gene signature for predicting survival outcomes in patients with colorectal cancer. Methods: Transcriptomic profiles together with corresponding clinical information from 461 patients with primary colon adenocarcinoma in the TCGA-COAD cohort were analyzed. After filtering and TMM normalization of RNA-sequencing data, 200 TP53 pathway genes obtained from the MSigDB Hallmark collection were screened using univariate Cox proportional hazards analysis. Eight prognostically relevant genes (VWA5A, SLC35D1, KLF4, RGS16, INHBB, FUCA1, KIF13B, and CDKN2A) 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 < 0.001). The calculated risk score remained significantly associated with survival outcome (HR > 1, p < 0.001), indicating its prognostic relevance. Predictive accuracy was supported by 12-month AUC values ranging from 0.75 to 0.85. Moreover, all eight genes displayed significant expression differences between the two risk groups, with KLF4 and FUCA1 exhibiting the strongest differential expression. Conclusions: The proposed TP53 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. Colorectal cancer, p53 pathway, prognostic signature, risk stratification, TCGA-COAD 0 0 http://humangeneticsgenomics.ir/browse.php?a_code=A-10-408-1&slc_lang=en&sid=1 Mohammad Zand m.zand653@yahoo.com 10031947532846001264 10031947532846001264 Yes Department of Biology, Shk.C., Islamic Azad University, Shahrekord, Iran Maryam Peymani m.peymani@iau.ac.ir 10031947532846001265 10031947532846001265 No Department of Biology, Shk.C., Islamic Azad University, Shahrekord, Iran Leila Rouhi Lrouhibiology@iau.ac.ir 10031947532846001266 10031947532846001266 No Department of Biology, Shk.C., Islamic Azad University, Shahrekord, Iran Ali Salehzadeh a.salehzadeh@iau.ac.ir 10031947532846001267 10031947532846001267 No Department of Biology, Ra.C., Islamic Azad University, Rasht, Iran