American Association for Cancer Research
can-23-1176_table_s2-revised_suppst2.xlsx (372.22 kB)

Table S2-revised from Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate

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posted on 2024-01-02, 08:20 authored by Jinge Zhao, Nanwei Xu, Sha Zhu, Ling Nie, Mengni Zhang, Linmao Zheng, Diming Cai, Xiaomeng Sun, Junru Chen, Jindong Dai, Yuchao Ni, Zhipeng Wang, Xingming Zhang, Jiayu Liang, Yuntian Chen, Xu Hu, Xiuyi Pan, Xiaoxue Yin, Haoyang Liu, Fengnian Zhao, Bei Zhang, Hao Chen, Jiashun Miao, Cong Qin, Xiaochen Zhao, Jin Yao, Zhenhua Liu, Banghua Liao, Qiang Wei, Xiang Li, Jiyan Liu, Allen C. Gao, Haojie Huang, Pengfei Shen, Ni Chen, Hao Zeng, Guangxi Sun

Table S2-revised


National Natural Science Foundation of China

1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University

Science and Technology Support Program of Sichuan Province

Clinical and Translational Medicine Research Project, Chinese Academy of Mediccal Sciences

Beijing Bethune Charitable Foundation

Postdoctoral Research and Development Fund of West China Hospital of Sichuan University



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. 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.

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