机构：[1]West China Hospital, Chengdu, China.四川大学华西医院[2]Department of Pathology and Laboratory of Pathology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, China.四川大学华西医院[3]Pathology Department, West China Hospital, West China Medical School,Sichuan University, Chengdu, China.四川大学华西医院[4]Department of Pathology, West China Hospital, Sichuan University, China.四川大学华西医院[5]GloriousMed Clinical Laboratory Co., Ltd., Shanghai, Shanghai, China.[6]institute of urology, chengdu, China.[7]West China Hospital of Sichuan University, Chengdu, Sichuan, China.四川大学华西医院[8]Sichuan University West China Hospital, Chengdu, China.[9]West China Hospital, West China Medical School, Chengdu, China.四川大学华西医院[10]3D Medicines Inc., shanghai, China.[11]3D Medicines Inc., Shanghai, China.[12]The Medical Department, 3D Medicines Inc. Shanghai, P.R. China, Shanghai, China.[13]West China Hospital of Sichuan University, chengdu, China.四川大学华西医院[14]West China Hospital of Sichuan University, Chengdu, China.四川大学华西医院[15]West China Hospital, West China Medical School, Sichuan University, Chengdu, China.四川大学华西医院[16]University of California, Davis, Sacramento, CA, United States.[17]Mayo Clinic, Rochester, MN, United States.
Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally co-exists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared to 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 pathological heterogeneity between IDC-P and PAC. Compared to co-existing PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 metastatic prostate cancer patients revealed that IDC-P carriers with lower risk 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.
基金：
This work was supported by the National Natural Science Foundation of China
(NSFC 82203110 [J.G.Z.], 82172785 [H.Z.], and 81974398 [H.Z.]), 1.3.5 project for
disciplines of excellence, West China Hospital, Sichuan University (ZYJC21020) [H.Z.],
Science and Technology Support Program of Sichuan Province (2021YFS0119) [H.Z.],
Clinical and Translational Medicine Research Project, Chinese Academy of Medical
Sciences (2022-12M-C&T-B-098) [H.Z.], Beijing Bethune Charitable Foundation
(mnzl202002 [H.Z.], mnzl202007 [P.F.S.]), and Postdoctoral Research and
Development Fund of West China Hospital of Sichuan University (2023HXBH024)
[J.G.Z.].
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|1 区医学
小类|2 区肿瘤学
最新[2023]版：
大类|1 区医学
小类|2 区肿瘤学
第一作者：
第一作者机构：[1]West China Hospital, Chengdu, China.
共同第一作者：
通讯作者：
通讯机构：[1]West China Hospital, Chengdu, China.[7]West China Hospital of Sichuan University, Chengdu, Sichuan, China.[9]West China Hospital, West China Medical School, Chengdu, China.[*1]#37 Guoxue Alley, Chengdu, Sichuan, China
推荐引用方式(GB/T 7714)：
Zhao Jinge,Zhu Sha,Nie Ling,et al.Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate[J].Cancer research.2023,doi:10.1158/0008-5472.CAN-23-1176.
APA：
Zhao Jinge,Zhu Sha,Nie Ling,Zhang Mengni,Zheng Linmao...&Sun Guangxi.(2023).Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.Cancer research,,
MLA：
Zhao Jinge,et al."Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate".Cancer research .(2023)
医学