Identification of novel gene-based risk score for prognosis in prostate cancer

Abstract Tumor carcinogenesis and progression result from multiple genetic alterations in tumor cells. However, reliable biomarkers for prostate cancer classification remain limited, often leading to either overtreatment or inadequate treatment. Additionally, effective biomarkers for selecting patie...

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Main Authors: Huangwei Huang, Xia Sun, Peixin Li, Haoxin Cai, Lejia Xu, Benkang Shi, Sifeng Qu
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-03800-3
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author Huangwei Huang
Xia Sun
Peixin Li
Haoxin Cai
Lejia Xu
Benkang Shi
Sifeng Qu
author_facet Huangwei Huang
Xia Sun
Peixin Li
Haoxin Cai
Lejia Xu
Benkang Shi
Sifeng Qu
author_sort Huangwei Huang
collection DOAJ
description Abstract Tumor carcinogenesis and progression result from multiple genetic alterations in tumor cells. However, reliable biomarkers for prostate cancer classification remain limited, often leading to either overtreatment or inadequate treatment. Additionally, effective biomarkers for selecting patients who may benefit from immunotherapy are still lacking. Using data from TCGA-PRAD, we established gene selection criteria to develop a gene-based risk score. We identified a novel gene risk panel comprising six genes (SSTR1, CA14, HJURP, KRTAP5-1, VGF, and COMP) for prostate cancer risk classification. Patients in the high-risk group were associated with poor prognosis. The gene panel exhibited significantly enhanced predictive accuracy for progression-free survival compared to conventional clinicopathological parameters, including T stage, N stage, primary Gleason score, and secondary Gleason score. High-risk patients exhibited a higher tumor mutation burden. Notably, immune activity of CD8 + T cells, NK cells, and the type II IFN response was significantly lower in the high-risk group, indicating a more immunosuppressive environment. Furthermore, a nomogram combining the gene-based risk score with T stage and histological grade was constructed. The expression of genes in the gene-based risk score was further validated using clinical samples, and VGF was found to play a significant role in prostate cancer progression. The nomogram could serve as a valuable biomarker for distinguishing between high-risk and low-risk of PFS prostate cancer patients and for selecting patients who might benefit from immunotherapy.
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spelling doaj-art-3de12cd0c66647dda97584effdd043362025-08-20T03:03:24ZengNature PortfolioScientific Reports2045-23222025-07-0115111710.1038/s41598-025-03800-3Identification of novel gene-based risk score for prognosis in prostate cancerHuangwei Huang0Xia Sun1Peixin Li2Haoxin Cai3Lejia Xu4Benkang Shi5Sifeng Qu6Department of Urology, Cheeloo College of Medicine, Qilu Hospital, Shandong UniversityDepartment of Pharmacology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityDepartment of Urology, Cheeloo College of Medicine, Qilu Hospital, Shandong UniversityDepartment of Pharmacology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityDepartment of Pharmacology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityDepartment of Urology, Cheeloo College of Medicine, Qilu Hospital, Shandong UniversityDepartment of Urology, Cheeloo College of Medicine, Qilu Hospital, Shandong UniversityAbstract Tumor carcinogenesis and progression result from multiple genetic alterations in tumor cells. However, reliable biomarkers for prostate cancer classification remain limited, often leading to either overtreatment or inadequate treatment. Additionally, effective biomarkers for selecting patients who may benefit from immunotherapy are still lacking. Using data from TCGA-PRAD, we established gene selection criteria to develop a gene-based risk score. We identified a novel gene risk panel comprising six genes (SSTR1, CA14, HJURP, KRTAP5-1, VGF, and COMP) for prostate cancer risk classification. Patients in the high-risk group were associated with poor prognosis. The gene panel exhibited significantly enhanced predictive accuracy for progression-free survival compared to conventional clinicopathological parameters, including T stage, N stage, primary Gleason score, and secondary Gleason score. High-risk patients exhibited a higher tumor mutation burden. Notably, immune activity of CD8 + T cells, NK cells, and the type II IFN response was significantly lower in the high-risk group, indicating a more immunosuppressive environment. Furthermore, a nomogram combining the gene-based risk score with T stage and histological grade was constructed. The expression of genes in the gene-based risk score was further validated using clinical samples, and VGF was found to play a significant role in prostate cancer progression. The nomogram could serve as a valuable biomarker for distinguishing between high-risk and low-risk of PFS prostate cancer patients and for selecting patients who might benefit from immunotherapy.https://doi.org/10.1038/s41598-025-03800-3Gene-based risk score Prostate cancer VGF Immune landscape 
spellingShingle Huangwei Huang
Xia Sun
Peixin Li
Haoxin Cai
Lejia Xu
Benkang Shi
Sifeng Qu
Identification of novel gene-based risk score for prognosis in prostate cancer
Scientific Reports
Gene-based risk score 
Prostate cancer 
VGF 
Immune landscape 
title Identification of novel gene-based risk score for prognosis in prostate cancer
title_full Identification of novel gene-based risk score for prognosis in prostate cancer
title_fullStr Identification of novel gene-based risk score for prognosis in prostate cancer
title_full_unstemmed Identification of novel gene-based risk score for prognosis in prostate cancer
title_short Identification of novel gene-based risk score for prognosis in prostate cancer
title_sort identification of novel gene based risk score for prognosis in prostate cancer
topic Gene-based risk score 
Prostate cancer 
VGF 
Immune landscape 
url https://doi.org/10.1038/s41598-025-03800-3
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