Prognostic risk modeling of endometrial cancer using programmed cell death-related genes: a comprehensive machine learning approach

Abstract Background Endometrial cancer represents a significant health challenge, with rising incidence and complex prognostic challenges. This study aimed to develop a robust predictive model integrating programmed cell death-related genes and advanced machine learning techniques. Methods Utilizing...

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Main Authors: Tianshu Chen, Yuhan Yang, Zhizhong Huang, Feng Pan, Zhendi Xiao, Kunxue Gong, Wenguang Huang, Liu Xu, Xueqin Liu, Caiyun Fang
Format: Article
Language:English
Published: Springer 2025-03-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02039-8
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author Tianshu Chen
Yuhan Yang
Zhizhong Huang
Feng Pan
Zhendi Xiao
Kunxue Gong
Wenguang Huang
Liu Xu
Xueqin Liu
Caiyun Fang
author_facet Tianshu Chen
Yuhan Yang
Zhizhong Huang
Feng Pan
Zhendi Xiao
Kunxue Gong
Wenguang Huang
Liu Xu
Xueqin Liu
Caiyun Fang
author_sort Tianshu Chen
collection DOAJ
description Abstract Background Endometrial cancer represents a significant health challenge, with rising incidence and complex prognostic challenges. This study aimed to develop a robust predictive model integrating programmed cell death-related genes and advanced machine learning techniques. Methods Utilizing transcriptomic data from TCGA-UCEC and GSE119041 datasets, we employed a comprehensive approach involving 117 machine learning algorithms. Key methodologies included differential gene expression analysis, weighted gene co-expression network analysis, functional enrichment studies, immune landscape evaluation, and multi-dimensional risk stratification. Results We identified 10 critical genes (PTGIS, TIMP3, SRPX, SNCA, HIC1, BAK1, STXBP2, TRIB3, RTKN2, E2F1) and constructed a prognostic model with superior predictive performance. The StepCox[forward] + plsRcox algorithm combination demonstrated excellent predictive accuracy (AUC > 0.8). Kaplan–Meier analysis revealed significant survival differences between high- and low-risk groups in both training (HR = 3.37, p < 0.001) and validation cohorts (HR = 2.05, p = 0.021). The model showed strong correlations with clinical characteristics, immune cell infiltration patterns, and potential therapeutic responses. Conclusions This study presents a novel, comprehensive approach to endometrial cancer prognosis, integrating machine learning and molecular insights to provide a more precise risk stratification tool with potential clinical translation.
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spelling doaj-art-c930af13a6284b54b462431507a8cdac2025-08-20T02:59:57ZengSpringerDiscover Oncology2730-60112025-03-0116111810.1007/s12672-025-02039-8Prognostic risk modeling of endometrial cancer using programmed cell death-related genes: a comprehensive machine learning approachTianshu Chen0Yuhan Yang1Zhizhong Huang2Feng Pan3Zhendi Xiao4Kunxue Gong5Wenguang Huang6Liu Xu7Xueqin Liu8Caiyun Fang9Department of Gynecology, Taihe Hospital, Hubei University of MedicineDepartment of Gynecology, Taihe Hospital, Hubei University of MedicineDepartment of Gynecology, Taihe Hospital, Hubei University of MedicineDepartment of Gynecology, Taihe Hospital, Hubei University of MedicineDepartment of Gynecology, Taihe Hospital, Hubei University of MedicineDepartment of Gynecology, Taihe Hospital, Hubei University of MedicineDepartment of Gynecology, Taihe Hospital, Hubei University of MedicineDepartment of Gynecology, Taihe Hospital, Hubei University of MedicineDepartment of Gynecology, Taihe Hospital, Hubei University of MedicineDepartment of Gynecology, Taihe Hospital, Hubei University of MedicineAbstract Background Endometrial cancer represents a significant health challenge, with rising incidence and complex prognostic challenges. This study aimed to develop a robust predictive model integrating programmed cell death-related genes and advanced machine learning techniques. Methods Utilizing transcriptomic data from TCGA-UCEC and GSE119041 datasets, we employed a comprehensive approach involving 117 machine learning algorithms. Key methodologies included differential gene expression analysis, weighted gene co-expression network analysis, functional enrichment studies, immune landscape evaluation, and multi-dimensional risk stratification. Results We identified 10 critical genes (PTGIS, TIMP3, SRPX, SNCA, HIC1, BAK1, STXBP2, TRIB3, RTKN2, E2F1) and constructed a prognostic model with superior predictive performance. The StepCox[forward] + plsRcox algorithm combination demonstrated excellent predictive accuracy (AUC > 0.8). Kaplan–Meier analysis revealed significant survival differences between high- and low-risk groups in both training (HR = 3.37, p < 0.001) and validation cohorts (HR = 2.05, p = 0.021). The model showed strong correlations with clinical characteristics, immune cell infiltration patterns, and potential therapeutic responses. Conclusions This study presents a novel, comprehensive approach to endometrial cancer prognosis, integrating machine learning and molecular insights to provide a more precise risk stratification tool with potential clinical translation.https://doi.org/10.1007/s12672-025-02039-8Endometrial cancerPrognostic modelingProgrammed cell deathMachine learningPrecision oncology
spellingShingle Tianshu Chen
Yuhan Yang
Zhizhong Huang
Feng Pan
Zhendi Xiao
Kunxue Gong
Wenguang Huang
Liu Xu
Xueqin Liu
Caiyun Fang
Prognostic risk modeling of endometrial cancer using programmed cell death-related genes: a comprehensive machine learning approach
Discover Oncology
Endometrial cancer
Prognostic modeling
Programmed cell death
Machine learning
Precision oncology
title Prognostic risk modeling of endometrial cancer using programmed cell death-related genes: a comprehensive machine learning approach
title_full Prognostic risk modeling of endometrial cancer using programmed cell death-related genes: a comprehensive machine learning approach
title_fullStr Prognostic risk modeling of endometrial cancer using programmed cell death-related genes: a comprehensive machine learning approach
title_full_unstemmed Prognostic risk modeling of endometrial cancer using programmed cell death-related genes: a comprehensive machine learning approach
title_short Prognostic risk modeling of endometrial cancer using programmed cell death-related genes: a comprehensive machine learning approach
title_sort prognostic risk modeling of endometrial cancer using programmed cell death related genes a comprehensive machine learning approach
topic Endometrial cancer
Prognostic modeling
Programmed cell death
Machine learning
Precision oncology
url https://doi.org/10.1007/s12672-025-02039-8
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