TY - JOUR
T1 - Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate
AU - Zhao, Jinge
AU - Xu, Nanwei
AU - Zhu, Sha
AU - Nie, Ling
AU - Zhang, Mengni
AU - Zheng, Linmao
AU - Cai, Diming
AU - Sun, Xiaomeng
AU - Chen, Junru
AU - Dai, Jindong
AU - Ni, Yuchao
AU - Wang, Zhipeng
AU - Zhang, Xingming
AU - Liang, Jiayu
AU - Chen, Yuntian
AU - Hu, Xu
AU - Pan, Xiuyi
AU - Yin, Xiaoxue
AU - Liu, Haoyang
AU - Zhao, Fengnian
AU - Zhang, Bei
AU - Chen, Hao
AU - Miao, Jiashun
AU - Qin, Cong
AU - Zhao, Xiaochen
AU - Yao, Jin
AU - Liu, Zhenhua
AU - Liao, Banghua
AU - Wei, Qiang
AU - Li, Xiang
AU - Liu, Jiyan
AU - Gao, Allen C.
AU - Huang, Haojie
AU - Shen, Pengfei
AU - Chen, Ni
AU - Zeng, Hao
AU - Sun, Guangxi
N1 - Publisher Copyright:
© 2024 American Association for Cancer Research Inc.. All rights reserved.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-23-1176
DO - 10.1158/0008-5472.CAN-23-1176
M3 - Article
C2 - 37847513
AN - SCOPUS:85178900486
SN - 0008-5472
VL - 184
SP - 154
EP - 167
JO - Cancer research
JF - Cancer research
IS - 1
ER -