A novel bone metastasis-related gene signature for predicting prognosis, anti-androgen resistance, and drug choice in prostate cancer

IF 3.4 2区医学 Q2 Medicine

Journal of Bone Oncology Pub Date : 2025-03-20 DOI:10.1016/j.jbo.2025.100673

Yu Luo , Xiaoqi Deng , Chengcheng Wei , Zhangcheng Liu , Liangdong Song , Kun Han , Yunfan Li , Jindong Zhang , Shuai Su , Delin Wang

{"title":"A novel bone metastasis-related gene signature for predicting prognosis, anti-androgen resistance, and drug choice in prostate cancer","authors":"Yu Luo , Xiaoqi Deng , Chengcheng Wei , Zhangcheng Liu , Liangdong Song , Kun Han , Yunfan Li , Jindong Zhang , Shuai Su , Delin Wang","doi":"10.1016/j.jbo.2025.100673","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Prostate cancer (PCa) often metastasizes to the bone, posing a significant clinical challenge. This study aims to develop a bone metastasis-related risk model for PCa.</div></div><div><h3>Methods</h3><div>Bone metastasis-related genes (BMRGs) were identified through a combination of differential gene expression analysis and WGCNA using GSE32269 and GSE77930 datasets. Consensus clustering analysis was employed to determine the significance of these genes in molecular subtyping of PCa. LASSO-Cox regression analysis was utilized to construct the bone metastasis-related prognostic gene signature (BMRPS). The predictive performance of BMRPS was assessed using ROC curves, Kaplan-Meier survival curves, and a predictive nomogram. The immune landscape heterogeneity of subgroups was analyzed using CIBERSORT, ESTIMATE, and xCell algorithms. Drug sensitivity and molecular docking analysis were performed to identify drugs associated with BMRPS.</div></div><div><h3>Results</h3><div>Forty-four BMRGs associated with the prognosis of PCa were identified. Consensus clustering revealed the pivotal role of these genes in stratifying PCa into three distinct prognostic clusters. The BMRPS, consisting of 14 BMRGs, demonstrated excellent predictive accuracy for prognosis and served as an independent prognostic factor in PCa. BMRPS effectively predicted the overall survival of bone metastatic PCa and differentiated bone metastasis from other metastatic types. BMRPS showed a close correlation with the immune landscape and immunotherapeutic response biomarkers. Additionally, BMRPS was associated with anti-androgen resistance, and AZD8186 was identified as a potential BMRPS-related drug that holds promise for personalized treatment in PCa.</div></div><div><h3>Conclusion</h3><div>BMRPS facilitates the prediction of prognosis and resistance to anti-androgens in PCa. It also offers insights into the molecular mechanisms of bone metastasis and aids in drug selection for the treatment of PCa.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"52 ","pages":"Article 100673"},"PeriodicalIF":3.4000,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Bone Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2212137425000144","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

Prostate cancer (PCa) often metastasizes to the bone, posing a significant clinical challenge. This study aims to develop a bone metastasis-related risk model for PCa.

Methods

Bone metastasis-related genes (BMRGs) were identified through a combination of differential gene expression analysis and WGCNA using GSE32269 and GSE77930 datasets. Consensus clustering analysis was employed to determine the significance of these genes in molecular subtyping of PCa. LASSO-Cox regression analysis was utilized to construct the bone metastasis-related prognostic gene signature (BMRPS). The predictive performance of BMRPS was assessed using ROC curves, Kaplan-Meier survival curves, and a predictive nomogram. The immune landscape heterogeneity of subgroups was analyzed using CIBERSORT, ESTIMATE, and xCell algorithms. Drug sensitivity and molecular docking analysis were performed to identify drugs associated with BMRPS.

Results

Forty-four BMRGs associated with the prognosis of PCa were identified. Consensus clustering revealed the pivotal role of these genes in stratifying PCa into three distinct prognostic clusters. The BMRPS, consisting of 14 BMRGs, demonstrated excellent predictive accuracy for prognosis and served as an independent prognostic factor in PCa. BMRPS effectively predicted the overall survival of bone metastatic PCa and differentiated bone metastasis from other metastatic types. BMRPS showed a close correlation with the immune landscape and immunotherapeutic response biomarkers. Additionally, BMRPS was associated with anti-androgen resistance, and AZD8186 was identified as a potential BMRPS-related drug that holds promise for personalized treatment in PCa.

Conclusion

BMRPS facilitates the prediction of prognosis and resistance to anti-androgens in PCa. It also offers insights into the molecular mechanisms of bone metastasis and aids in drug selection for the treatment of PCa.

Abstract Image

查看原文本刊更多论文

一种预测前列腺癌预后、抗雄激素抵抗和药物选择的新的骨转移相关基因标记

目的前列腺癌（PCa）经常转移到骨，这是一个重大的临床挑战。本研究旨在建立前列腺癌骨转移相关风险模型。方法使用GSE32269和GSE77930数据集，通过差异基因表达分析和WGCNA相结合，鉴定骨转移相关基因（BMRGs）。采用一致聚类分析来确定这些基因在前列腺癌分子分型中的意义。采用LASSO-Cox回归分析构建骨转移相关预后基因特征（BMRPS）。采用ROC曲线、Kaplan-Meier生存曲线和预测nomogram来评估BMRPS的预测性能。使用CIBERSORT、ESTIMATE和xCell算法分析亚组免疫景观异质性。通过药物敏感性和分子对接分析鉴定与BMRPS相关的药物。结果共发现44个与前列腺癌预后相关的BMRGs。共识聚类揭示了这些基因在将PCa分为三个不同的预后集群中的关键作用。BMRPS由14个BMRGs组成，具有良好的预后预测准确性，可作为PCa的独立预后因素。BMRPS可有效预测骨转移性前列腺癌的总生存率，并可将骨转移与其他转移类型区分开来。BMRPS与免疫景观和免疫治疗反应生物标志物密切相关。此外，BMRPS与抗雄激素耐药性相关，AZD8186被确定为潜在的BMRPS相关药物，有望用于PCa的个性化治疗。结论bmrps有助于预测前列腺癌的预后和抗雄激素耐药性。它也提供了深入了解骨转移的分子机制和辅助药物选择治疗前列腺癌。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Bone Oncology ONCOLOGY-

CiteScore

7.20

自引率

2.90%

发文量

审稿时长

34 days

期刊介绍： The Journal of Bone Oncology is a peer-reviewed international journal aimed at presenting basic, translational and clinical high-quality research related to bone and cancer. As the first journal dedicated to cancer induced bone diseases, JBO welcomes original research articles, review articles, editorials and opinion pieces. Case reports will only be considered in exceptional circumstances and only when accompanied by a comprehensive review of the subject. The areas covered by the journal include: Bone metastases (pathophysiology, epidemiology, diagnostics, clinical features, prevention, treatment) Preclinical models of metastasis Bone microenvironment in cancer (stem cell, bone cell and cancer interactions) Bone targeted therapy (pharmacology, therapeutic targets, drug development, clinical trials, side-effects, outcome research, health economics) Cancer treatment induced bone loss (epidemiology, pathophysiology, prevention and management) Bone imaging (clinical and animal, skeletal interventional radiology) Bone biomarkers (clinical and translational applications) Radiotherapy and radio-isotopes Skeletal complications Bone pain (mechanisms and management) Orthopaedic cancer surgery Primary bone tumours Clinical guidelines Multidisciplinary care Keywords: bisphosphonate, bone, breast cancer, cancer, CTIBL, denosumab, metastasis, myeloma, osteoblast, osteoclast, osteooncology, osteo-oncology, prostate cancer, skeleton, tumour.