Integrated analysis of single-cell and bulk transcriptomes uncovers clinically relevant molecular subtypes in human prostate cancer.

IF 7 2区 医学 Q1 ONCOLOGY Chinese Journal of Cancer Research Pub Date : 2025-01-30 DOI:10.21147/j.issn.1000-9604.2025.01.07
Tao Ding, Lina He, Guowen Lin, Lei Xu, Yanjun Zhu, Xinan Wang, Xuefei Liu, Jianming Guo, Fanghong Lei, Zhixiang Zuo, Jianghua Zheng
{"title":"Integrated analysis of single-cell and bulk transcriptomes uncovers clinically relevant molecular subtypes in human prostate cancer.","authors":"Tao Ding, Lina He, Guowen Lin, Lei Xu, Yanjun Zhu, Xinan Wang, Xuefei Liu, Jianming Guo, Fanghong Lei, Zhixiang Zuo, Jianghua Zheng","doi":"10.21147/j.issn.1000-9604.2025.01.07","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Prostate cancer (PCa) is a complex disease characterized by diverse cellular ecosystems within the tumor microenvironment (TME) and high tumor heterogeneity, which challenges clinically stratified management and reinforces the need for novel strategies to fight against castration-resistant PCa (CRPC).</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing (scRNA-seq) on 10 untreated primary PCa tissues and integrated public scRNA-seq resources from three normal prostate tissues, two untreated primary PCa tissues, and six CRPC tumors to portray a comprehensive cellular and molecular interaction atlas of PCa. We further integrated the single-cell and bulk transcriptomes of PCa to establish a molecular classification system.</p><p><strong>Results: </strong>scRNA-seq profiles revealed substantial inter- and intra-tumoral heterogeneity across different cell subpopulations in untreated PCa and CRPC tumors. In the malignant epithelial reservoir, cells evolved along decoupled paths in treatment-naive PCa and CRPC tumors, and distinct transcriptional reprogramming processes were activated, highlighting anti-androgen therapy-induced lineage plasticity. Based on the specifically expressed markers of the epithelial subpopulations, we conducted unsupervised clustering analysis in The Cancer Genome Atlas prostate adenocarcinoma (TCGA-PRAD) cohort and identified three molecularly and clinically distinct subtypes. The C1 subtype, characterized by high enrichment of CRPC-enriched epithelial cells, had a high risk of rapid development of anti-androgen resistance and might require active surveillance and additional promising intervention treatments, such as integrin A3 (<i>ITGA3</i>) + integrin B1 (<i>ITGB1</i>) inhibition. The C2 subtype resembled the immune-modulated subtype that was most likely to benefit from anti-LAG3 immunotherapy. The C3 subtype had a favorable prognosis.</p><p><strong>Conclusions: </strong>Our study provides a comprehensive and high-resolution landscape of the intricate architecture of the PCa TME, and our trichotomic molecular taxonomy could help facilitate precision oncology.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"37 1","pages":"90-114"},"PeriodicalIF":7.0000,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893346/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Journal of Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21147/j.issn.1000-9604.2025.01.07","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Objective: Prostate cancer (PCa) is a complex disease characterized by diverse cellular ecosystems within the tumor microenvironment (TME) and high tumor heterogeneity, which challenges clinically stratified management and reinforces the need for novel strategies to fight against castration-resistant PCa (CRPC).

Methods: We performed single-cell RNA sequencing (scRNA-seq) on 10 untreated primary PCa tissues and integrated public scRNA-seq resources from three normal prostate tissues, two untreated primary PCa tissues, and six CRPC tumors to portray a comprehensive cellular and molecular interaction atlas of PCa. We further integrated the single-cell and bulk transcriptomes of PCa to establish a molecular classification system.

Results: scRNA-seq profiles revealed substantial inter- and intra-tumoral heterogeneity across different cell subpopulations in untreated PCa and CRPC tumors. In the malignant epithelial reservoir, cells evolved along decoupled paths in treatment-naive PCa and CRPC tumors, and distinct transcriptional reprogramming processes were activated, highlighting anti-androgen therapy-induced lineage plasticity. Based on the specifically expressed markers of the epithelial subpopulations, we conducted unsupervised clustering analysis in The Cancer Genome Atlas prostate adenocarcinoma (TCGA-PRAD) cohort and identified three molecularly and clinically distinct subtypes. The C1 subtype, characterized by high enrichment of CRPC-enriched epithelial cells, had a high risk of rapid development of anti-androgen resistance and might require active surveillance and additional promising intervention treatments, such as integrin A3 (ITGA3) + integrin B1 (ITGB1) inhibition. The C2 subtype resembled the immune-modulated subtype that was most likely to benefit from anti-LAG3 immunotherapy. The C3 subtype had a favorable prognosis.

Conclusions: Our study provides a comprehensive and high-resolution landscape of the intricate architecture of the PCa TME, and our trichotomic molecular taxonomy could help facilitate precision oncology.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
求助全文
约1分钟内获得全文 去求助
来源期刊
自引率
9.80%
发文量
1726
审稿时长
4.5 months
期刊介绍: Chinese Journal of Cancer Research (CJCR; Print ISSN: 1000-9604; Online ISSN:1993-0631) is published by AME Publishing Company in association with Chinese Anti-Cancer Association.It was launched in March 1995 as a quarterly publication and is now published bi-monthly since February 2013. CJCR is published bi-monthly in English, and is an international journal devoted to the life sciences and medical sciences. It publishes peer-reviewed original articles of basic investigations and clinical observations, reviews and brief communications providing a forum for the recent experimental and clinical advances in cancer research. This journal is indexed in Science Citation Index Expanded (SCIE), PubMed/PubMed Central (PMC), Scopus, SciSearch, Chemistry Abstracts (CA), the Excerpta Medica/EMBASE, Chinainfo, CNKI, CSCI, etc.
期刊最新文献
CT-based radiomics-deep learning model predicts occult lymph node metastasis in early-stage lung adenocarcinoma patients: A multicenter study. Deep learning-based multi-task prediction of response to neoadjuvant chemotherapy using multiscale whole slide images in breast cancer: A multicenter study. Improving neuroblastoma risk prediction through a polygenic risk score derived from genome-wide association study-identified loci. Integrated analysis of single-cell and bulk transcriptomes uncovers clinically relevant molecular subtypes in human prostate cancer. Prophylactic hyperthermic intraperitoneal chemotherapy in patients with locally advanced gastric cancer after curative surgery: Final results of a phase II trial.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1