Development and validation of a prognostic model of transcription factors in colon adenocarcinoma

LIN Chen; LU Chenjia; XIANG Yao

doi:10.3969/j.issn.1009-0460.2025.08.009

Abstract：Objective To obtain the transcription factor prognosis model of colon adenocarcinoma(COAD),providing a theoretical basis for evaluating the survival risk of patients with COAD.Methods the clinical information and RNA seq data of patients with COAD from the Cancer Genome Atlas(TCGA)database was downloaded to obtain differential transcription factor genes and perform GO and KEGG function enrichment analysis.Univariate and multivariate Cox proportional risk regression models were used to develop transcription factor models with prognostic value.Kaplan Meier method was used to analyze the survival status of high-risk and low-risk patients.ROC curve was used to assess the accuracy of risk scores and the sensitivity and specificity of clinical pathological parameters and risk models for predicting the prognosis of colon adenocarcinoma patients.50%of the cases were randomly selected from the sample for internal validation.Independent prognostic factors such as patient's age,sex,TNM stage,T stage,N stage and risk score were verified by using univariate and multivariate Cox regression analysis,and multivariate Cox regression analysis was used to evaluate the nomograph model of clinical pathological parameters and risk score.Results A total of 131 differentially expressed TFs were identified.Through univariate and multivariate Cox regression analysis,three transcription factors(FOXS1,HSF4,and LBX2)were identified as risk factors affecting the prognosis of COAD patients.The linkage analysis of risk factors using multiple Cox regression showed that high-risk patients had higher risk scores,while low-risk patients had higher risk scores,and similar results were obtained in the internal testing group.The risk score of the model showed that the overall survival time of patients in the high-risk group was shorter than that in the low-risk group(P<0.001),which was also validated in the internal testing group(P<0.001).The area under the ROC curve(AUC value)of this risk scoring model was 0.719,0.773,0.773,and 0.694 at 1 year,3 years,5 years,and 10 years,respectively.The internal validation group had areas of 0.714,0.783,0.783,and 0.668,and the AUC value of clinical pathological features such as TNM stage,age,gender,T stage,and N stage was 0.783,0.278,0.773,0.655,0.627,and 0.639 at 3-year survival rates,while the internal validation group had areas of 0.773,0.339,0.657,0.577,0.609,and 0.706 at 3-year survival rates.The results of the multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for COAD(HR=2.160,95%CI:1.370-3.406,P=0.001).The concordance index of the nomogram prediction model constructed based on the multivariate Cox regression analysis was 0.878.Conclusion The development and validation of transcription factor prognostic risk models are of great significance for identifying subgroups of patients with high or low risk of COAD.