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Cai, Diming

0000-0002-6733-6727

Mayo Clinic

Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, P.R. China.

Citations 1

Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate
Zhao, Jinge , Xu, Nanwei , Nie, Ling , Zhang, Mengni , Zheng, Linmao , Cai, Diming , Sun, Xiaomeng , Chen, Junru , Dai, Jindong , Ni, Yuchao , Wang, Zhipeng , Zhang, Xingming , Liang, Jiayu, Chen, Yuntian , Pan, Xiuyi , Yin, Xiaoxue , Liu, Haoyang , Zhao, Fengnian , Zhang, Bei , Chen, Hao , Miao, Jiashun , Qin, Cong , Zhao, Xiaochen , Yao, Jin , Liu, Zhenhua , Liao, Banghua , Wei, Qiang , Shen, Pengfei , Chen, Ni , Zeng, Hao , Sun, Guangxi , Zhu, Sha , Nie, Ling , Zhang, Mengni , Zheng, Linmao , Cai, Diming , Sun, Xiaomeng , Chen, Junru , Dai, Jindong , Ni, Yuchao , Wang, Zhipeng , Zhang, Xingming , Liang, Jiayu , Chen, Yuntian , Hu, Xu , Pan, Xiuyi , Yin, Xiaoxue , Liu, Haoyang , Zhao, Fengnian , Zhang, Bei , Chen, Hao , Miao, Jiashun , Qin, Cong , Zhao, Xiaochen , Yao, Jin , Liu, Zhenhua , Liao, Banghua , Wei, Qiang , Li, Xiang , Liu, Zhenhua , Gao, Allen C , Huang, Rui , Shen, Pengfei , Chen, Ni , Zeng, Hao , Sun, Guangxi , Zhu, Sha , Liu, Jiyan , Huang, Haojie

Cancer Research | October 17, 2023 | Volume: 84 | Issue: 1 | Pages: 154-167

10.1158/0008-5472.can-23-1176 Get It

Abstract Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis–associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1–4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation–associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P. Significance: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.