Yuan Shao, Xiaolei Zhang, Yinchi Zhang, Zihao Liu, Zhen Yang, Yang Liu, Hua Huang, Zeyuan Wang, Zhinan Fu, Yong Wang
{"title":"色氨酸代谢相关风险模型及分子亚型预测前列腺癌术后生化复发的建立与验证","authors":"Yuan Shao, Xiaolei Zhang, Yinchi Zhang, Zihao Liu, Zhen Yang, Yang Liu, Hua Huang, Zeyuan Wang, Zhinan Fu, Yong Wang","doi":"10.21037/tau-2025-39","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Biochemical recurrence (BCR) following radical prostatectomy (RP) remains a major challenge in prostate cancer (PCa) management. Tryptophan metabolism plays a pivotal role in tumor progression and immune modulation. This study aimed to develop and validate a tryptophan metabolism-related risk model and molecular subtypes to predict BCR in PCa patients after RP.</p><p><strong>Methods: </strong>The Cancer Genome Atlas-Prostate Adenocarcinoma (TCGA-PRAD) dataset, including 421 PCa patients, was analyzed to identify key tryptophan metabolism-related genes (TMRGs) using differential expression, univariate Cox, and the least absolute shrinkage and selection operator (LASSO) regression analyses. The tryptophan metabolism-related risk model was constructed through multivariate Cox regression, and tryptophan metabolism-related molecular subtypes were established using consensus clustering. External validation was conducted using an independent dataset, while immunohistochemistry (IHC) and single-cell sequencing further confirmed TMRG expression patterns and their roles in the tumor microenvironment (TME).</p><p><strong>Results: </strong>The tryptophan metabolism-related risk model and molecular subtypes effectively stratified PCa patients into low- and high-risk groups or two molecular subtypes. High-risk PCa patients (n=211) and those in Cluster 1 (n=261) exhibited significantly poorer biochemical recurrence-free survival (BRFS) and distinct clinicopathological features, immune infiltration profiles, and TME characteristics. External validation confirmed the robustness of the tryptophan metabolism-related risk model and molecular subtypes. IHC and single-cell sequencing highlighted the expression patterns of TMRGs and their regulatory roles in the TME.</p><p><strong>Conclusions: </strong>This study established and validated tryptophan metabolism-related risk scores and molecular subtypes as reliable predictors of BCR in PCa patients after RP. These findings provide a foundation for personalized follow-up and treatment strategies, contributing to improved clinical outcomes in PCa management.</p>","PeriodicalId":23270,"journal":{"name":"Translational andrology and urology","volume":"14 4","pages":"1082-1110"},"PeriodicalIF":1.7000,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076229/pdf/","citationCount":"0","resultStr":"{\"title\":\"Development and validation of tryptophan metabolism-related risk model and molecular subtypes for predicting postoperative biochemical recurrence in prostate cancer.\",\"authors\":\"Yuan Shao, Xiaolei Zhang, Yinchi Zhang, Zihao Liu, Zhen Yang, Yang Liu, Hua Huang, Zeyuan Wang, Zhinan Fu, Yong Wang\",\"doi\":\"10.21037/tau-2025-39\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Biochemical recurrence (BCR) following radical prostatectomy (RP) remains a major challenge in prostate cancer (PCa) management. Tryptophan metabolism plays a pivotal role in tumor progression and immune modulation. This study aimed to develop and validate a tryptophan metabolism-related risk model and molecular subtypes to predict BCR in PCa patients after RP.</p><p><strong>Methods: </strong>The Cancer Genome Atlas-Prostate Adenocarcinoma (TCGA-PRAD) dataset, including 421 PCa patients, was analyzed to identify key tryptophan metabolism-related genes (TMRGs) using differential expression, univariate Cox, and the least absolute shrinkage and selection operator (LASSO) regression analyses. The tryptophan metabolism-related risk model was constructed through multivariate Cox regression, and tryptophan metabolism-related molecular subtypes were established using consensus clustering. External validation was conducted using an independent dataset, while immunohistochemistry (IHC) and single-cell sequencing further confirmed TMRG expression patterns and their roles in the tumor microenvironment (TME).</p><p><strong>Results: </strong>The tryptophan metabolism-related risk model and molecular subtypes effectively stratified PCa patients into low- and high-risk groups or two molecular subtypes. High-risk PCa patients (n=211) and those in Cluster 1 (n=261) exhibited significantly poorer biochemical recurrence-free survival (BRFS) and distinct clinicopathological features, immune infiltration profiles, and TME characteristics. External validation confirmed the robustness of the tryptophan metabolism-related risk model and molecular subtypes. IHC and single-cell sequencing highlighted the expression patterns of TMRGs and their regulatory roles in the TME.</p><p><strong>Conclusions: </strong>This study established and validated tryptophan metabolism-related risk scores and molecular subtypes as reliable predictors of BCR in PCa patients after RP. These findings provide a foundation for personalized follow-up and treatment strategies, contributing to improved clinical outcomes in PCa management.</p>\",\"PeriodicalId\":23270,\"journal\":{\"name\":\"Translational andrology and urology\",\"volume\":\"14 4\",\"pages\":\"1082-1110\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-04-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076229/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational andrology and urology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/tau-2025-39\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"ANDROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational andrology and urology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tau-2025-39","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/27 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ANDROLOGY","Score":null,"Total":0}
Development and validation of tryptophan metabolism-related risk model and molecular subtypes for predicting postoperative biochemical recurrence in prostate cancer.
Background: Biochemical recurrence (BCR) following radical prostatectomy (RP) remains a major challenge in prostate cancer (PCa) management. Tryptophan metabolism plays a pivotal role in tumor progression and immune modulation. This study aimed to develop and validate a tryptophan metabolism-related risk model and molecular subtypes to predict BCR in PCa patients after RP.
Methods: The Cancer Genome Atlas-Prostate Adenocarcinoma (TCGA-PRAD) dataset, including 421 PCa patients, was analyzed to identify key tryptophan metabolism-related genes (TMRGs) using differential expression, univariate Cox, and the least absolute shrinkage and selection operator (LASSO) regression analyses. The tryptophan metabolism-related risk model was constructed through multivariate Cox regression, and tryptophan metabolism-related molecular subtypes were established using consensus clustering. External validation was conducted using an independent dataset, while immunohistochemistry (IHC) and single-cell sequencing further confirmed TMRG expression patterns and their roles in the tumor microenvironment (TME).
Results: The tryptophan metabolism-related risk model and molecular subtypes effectively stratified PCa patients into low- and high-risk groups or two molecular subtypes. High-risk PCa patients (n=211) and those in Cluster 1 (n=261) exhibited significantly poorer biochemical recurrence-free survival (BRFS) and distinct clinicopathological features, immune infiltration profiles, and TME characteristics. External validation confirmed the robustness of the tryptophan metabolism-related risk model and molecular subtypes. IHC and single-cell sequencing highlighted the expression patterns of TMRGs and their regulatory roles in the TME.
Conclusions: This study established and validated tryptophan metabolism-related risk scores and molecular subtypes as reliable predictors of BCR in PCa patients after RP. These findings provide a foundation for personalized follow-up and treatment strategies, contributing to improved clinical outcomes in PCa management.
期刊介绍：
ranslational Andrology and Urology (Print ISSN 2223-4683; Online ISSN 2223-4691; Transl Androl Urol; TAU) is an open access, peer-reviewed, bi-monthly journal (quarterly published from Mar.2012 - Dec. 2014). The main focus of the journal is to describe new findings in the field of translational research of Andrology and Urology, provides current and practical information on basic research and clinical investigations of Andrology and Urology. Specific areas of interest include, but not limited to, molecular study, pathology, biology and technical advances related to andrology and urology. Topics cover range from evaluation, prevention, diagnosis, therapy, prognosis, rehabilitation and future challenges to urology and andrology. Contributions pertinent to urology and andrology are also included from related fields such as public health, basic sciences, education, sociology, and nursing.
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