Androgen Receptor Splice Variant 7 Predicts Shorter Response in Patients with Metastatic Hormone-sensitive Prostate Cancer Receiving Androgen Deprivation Therapy

被引：34

作者：

Li, Heng ^{[1
,2
]}

Zhang, Yucong ^{[3
]}

Li, Dong ^{[4
]}

Ma, Xin ^{[5
]}

Xu, Kai ^{[6
]}

Ding, Beichen ^{[7
]}

Li, Hongzhao ^{[5
]}

Wang, Zhize ^{[8
]}

Ouyang, Wei ^{[1
,2
]}

Long, Gongwei ^{[1
,2
]}

Zeng, Jin ^{[9
]}

Liu, Haoran ^{[1
,2
]}

Yan, Libin ^{[8
]}

Zhang, Yangjun ^{[1
,2
]}

Liu, Zheng ^{[1
,2
]}

Guan, Wei ^{[1
,2
]}

Hu, Zhiquan ^{[1
,2
]}

Liu, Cong ^{[10
]}

Wan, Jie ^{[10
]}

Wang, Guoping ^{[10
]}

Pu, Xiaoyong ^{[11
]}

Zhang, Minghui ^{[11
]}

Guo, Linlang ^{[12
]}

An, Ruihua ^{[7
]}

Qi, Jiping ^{[13
]}

Guo, Aitao ^{[14
]}

Ye, Zhangqun ^{[1
,2
]}

Liu, Jiumin ^{[4
]}

Zhang, Xu ^{[5
]}

Xu, Hua ^{[1
,2
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Urol, Wuhan 430030, Hubei, Peoples R China

[2] Inst Urol Hubei Prov, Wuhan 430030, Hubei, Peoples R China

[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Geriatr, Tongji Hosp, Wuhan, Peoples R China

[4] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Dept Urol, Guangzhou, Peoples R China

[5] Chinese Peoples Liberat Army Gen Hosp, Dept Urol, Beijing 100039, Peoples R China

[6] Southern Med Univ, Dept Urol, Zhujiang Hosp, Guangzhou, Peoples R China

[7] Harbin Med Univ, Dept Urol, Affiliated Hosp 1, Harbin, Peoples R China

[8] Zhejiang Univ, Affiliated Hosp 1, Coll Med, Dept Urol, Hangzhou, Peoples R China

[9] Nanchang Univ, Dept Urol, Affiliated Hosp 1, Nanchang, Jiangxi, Peoples R China

[10] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pathol, Tongji Hosp, Wuhan, Peoples R China

[11] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Dept Pathol, Guangzhou, Peoples R China

[12] Southern Med Univ, Dept Pathol, Zhujiang Hosp, Guangzhou, Peoples R China

[13] Harbin Med Univ, Dept Pathol, Affiliated Hosp 1, Harbin, Peoples R China

[14] Chinese Peoples Liberat Army Gen Hosp, Dept Pathol, Beijing, Peoples R China

来源：

EUROPEAN UROLOGY | 2021年 / 79卷 / 06期

关键词：

Androgen receptor splice variant 7; Androgen deprivation therapy; Metastatic hormone-sensitive prostate cancer; Prospective cohort study; Immunohistochemical staining; ABIRATERONE; RESISTANCE; AR-V7; PROGRESSION; STATISTICS;

D O I：

10.1016/j.eururo.2021.01.037

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Whether AR-V7 expression can predict the response in patients with metastatic hormone-sensitive prostate cancer (mHSPC) who receive androgen deprivation therapy (ADT) remains to be explored. Objective: To evaluate the predictive value of AR-V7 expression in the prognosis of mHSPC patients receiving ADT. Design, setting, and participants: In this multicenter prospective cohort study, 310 mHSPC patients commencing ADT were enrolled. Standard immunohistochemical staining was used to assess AR-V7 protein expression in biopsy tissues collected before initiation of ADT. Outcome measurements and statistical analysis: Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate associations of AR-V7 status (positive vs negative) with progression-free survival (PFS) and overall survival (OS). Results and limitations: Sixty-four (21%) patients were AR-V7-positive and 246 (79%) patients were AR-V7-negative. The median follow-up for patients not confirmed dead was 25 mo (interquartile range 10-30). Compared to AR-V7-negative patients, AR-V7-positive patients had significantly shorter PFS (hazard ratio [HR] 47.39, 95% confidence interval [CI] 25.83-86.94) and OS (HR 3.57, 95% CI 1.46-8.72). In multivariable analysis, AR-V7 was an independent predictive factor (HR 7.61, 95% CI 5.24-11.06) for shorter PFS. Limitations include the sample size and follow-up period. Conclusions: AR-V7 expression in primary cancer tissue is correlated with poor prognosis for mHSPC patients receiving ADT. Patient summary: In this study of men with metastatic hormone-sensitive prostate cancer, AR-V7 protein expression in primary cancer tissue was associated with poor outcomes on androgen deprivation therapy. (C) 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.

引用

页码：879 / 886

页数：8

共 28 条

[1] Clinical Significance of Androgen Receptor Splice Variant-7 mRNA Detection in Circulating Tumor Cells of Men With Metastatic Castration- Resistant Prostate Cancer Treated With First- and Second-Line Abiraterone and Enzalutamide [J].

Antonarakis, Emmanuel S. ;

Lu, Changxue ;

Luber, Brandon ;

Wang, Hao ;

Chen, Yan ;

Zhu, Yezi ;

Silberstein, John L. ;

Taylor, Maritza N. ;

Maughan, Benjamin L. ;

Denmeade, Samuel R. ;

Pienta, Kenneth J. ;

Paller, Channing J. ;

Carducci, Michael A. ;

Eisenberger, Mario A. ;

Luo, Jun .

JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (19) :2149-+

[2] Androgen Receptor Splice Variant 7 and Efficacy of Taxane Chemotherapy in Patients With Metastatic Castration-Resistant Prostate Cancer [J].

Antonarakis, Emmanuel S. ;

Lu, Changxue ;

Luber, Brandon ;

Wang, Hao ;

Chen, Yan ;

Nakazawa, Mary ;

Nadal, Rosa ;

Paller, Channing J. ;

Denmeade, Samuel R. ;

Carducci, Michael A. ;

Eisenberger, Mario A. ;

Luo, Jun .

JAMA ONCOLOGY, 2015, 1 (05) :582-591

[3] AR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer [J].

Antonarakis, Emmanuel S. ;

Lu, Changxue ;

Wang, Hao ;

Luber, Brandon ;

Nakazawa, Mary ;

Roeser, Jeffrey C. ;

Chen, Yan ;

Mohammad, Tabrez A. ;

Chen, Yidong ;

Fedor, Helen L. ;

Lotan, Tamara L. ;

Zheng, Qizhi ;

De Marzo, Angelo M. ;

Isaacs, John T. ;

Isaacs, William B. ;

Nadal, Rosa ;

Paller, Channing J. ;

Denmeade, Samuel R. ;

Carducci, Michael A. ;

Eisenberger, Mario A. ;

Luo, Jun .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (11) :1028-1038

[4] Cancer Statistics in China, 2015 [J].

Chen, Wanqing ;

Zheng, Rongshou ;

Baade, Peter D. ;

Zhang, Siwei ;

Zeng, Hongmei ;

Bray, Freddie ;

Jemal, Ahmedin ;

Yu, Xue Qin ;

He, Jie .

CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132

[5] Targeting androgen receptor versus targeting androgens to suppress castration resistant prostate cancer [J].

Guo, Changcheng ;

Yeh, Shuyuan ;

Niu, Yuanjie ;

Li, Gonghui ;

Zheng, Junhua ;

Li, Lei ;

Chang, Chawnshang .

CANCER LETTERS, 2017, 397 :133-143

[6] A Novel Androgen Receptor Splice Variant Is Up-regulated during Prostate Cancer Progression and Promotes Androgen Depletion-Resistant Growth [J].

Guo, Zhiyong ;

Yang, Xi ;

Sun, Feng ;

Jiang, Richeng ;

Linn, Douglas E. ;

Chen, Hege ;

Chen, Hegang ;

Kong, Xiangtian ;

Melamed, Jonathan ;

Tepper, Clifford G. ;

Kung, Hsing-Jien ;

Brodie, Angela M. H. ;

Edwards, Joanne ;

Qiu, Yun .

CANCER RESEARCH, 2009, 69 (06) :2305-2313

[7] Expression of Androgen Receptor Splice Variants in Prostate Cancer Bone Metastases is Associated with Castration-Resistance and Short Survival [J].

Hornberg, Emma ;

Ylitalo, Erik Bovinder ;

Crnalic, Sead ;

Antti, Henrik ;

Stattin, Par ;

Widmark, Anders ;

Bergh, Anders ;

Wikstrom, Pernilla .

PLOS ONE, 2011, 6 (04)

[8] A Snapshot of the Expression Signature of Androgen Receptor Splicing Variants and Their Distinctive Transcriptional Activities [J].

Hu, Rong ;

Isaacs, William B. ;

Luo, Jun .

PROSTATE, 2011, 71 (15) :1656-1667

[9] Ligand-Independent Androgen Receptor Variants Derived from Splicing of Cryptic Exons Signify Hormone-Refractory Prostate Cancer [J].

Hu, Rong ;

Dunn, Thomas A. ;

Wei, Shuanzeng ;

Isharwal, Sumit ;

Veltri, Robert W. ;

Humphreys, Elizabeth ;

Han, Misop ;

Partin, Alan W. ;

Vessella, Robert L. ;

Isaacs, William B. ;

Bova, G. Steven ;

Luo, Jun .

CANCER RESEARCH, 2009, 69 (01) :16-22

[10]

Huggins C, 1972, CA Cancer J Clin, V22, P232, DOI 10.3322/canjclin.22.4.232

← 1 2 3 →