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

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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.

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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.