Expression of ISL1 and its partners in prostate cancer progression and neuroendocrine differentiation

被引:5
作者
Alshalalfa, Mohammed [1 ]
Abou-Ouf, Hatem [2 ,3 ]
Davicioni, Elai [4 ]
Karnes, R. Jeffrey [5 ]
Alhajj, Reda [6 ]
Bismar, Tarek A. [1 ,2 ,3 ,7 ]
机构
[1] Prostate Canc Ctr, Calgary, AB, Canada
[2] Univ Calgary, Cumming Sch Med, Dept Pathol & Lab Med, Calgary, AB, Canada
[3] Univ Calgary, Arnie Charbonneau Canc Inst, Calgary, AB, Canada
[4] Decipher Biosci Inc, Vancouver, BC, Canada
[5] Mayo Clin, Dept Urol, Rochester, MN USA
[6] Univ Calgary, Dept Comp Sci, Calgary, AB, Canada
[7] Rockyview Gen Hosp, Dept Pathol & Lab Med, Calgary, AB T2V 1P9, Canada
关键词
ISL1; MEIS; Biomarker; Prostate cancer; Neuroendocrine; GENOMIC CLASSIFIER; GASTRIC-CANCER; VALIDATION; METASTASIS; SIGNATURE; GENES; MEIS2; MEN;
D O I
10.1007/s00432-021-03634-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Introduction and objectives ISL1 serves as a biomarker of metastasis and neuroendocrine neoplasia in multiple tumors. However, the expression and relation of ISL1 to other biomarkers in prostate cancer have not been fully elucidated. Here, we characterize the expression of ISL1 and its partners in PCa and document its association to disease progression and post castration resistance neuroendocrine differentiation. Methods The expression of ISL1 was interrogated in > 6000 primary samples from the Decipher GRID registry and 250 mCRPC samples to assess its prognostic value and relation to neuroendocrine differentiation. Results ISL1 was highly correlated to MEIS genes and other genes related to cell motility. ISL1 down-regulation in PCa was associated with cancer progression, aggressive primary tumors, and metastatic outcome. We found that ISL1 is highly correlated to MEIS genes across multiple primary PCa and mCRPC cohorts. The expression of ISL1 and MEIS genes were significantly and inversely related to metastasis-free survival and lethal disease, and were downregulated in CRPC and hormone naive metastatic tumors but showed upregulation in neuroendocrine tumors. Co-immunoprecipitation showed MEIS2 and ISL1 interacting with each supporting their role in modulating transcriptional regulation and nominating this complex for potential targeted therapy. Conclusions ISL1 complex with MEIS2 serves a critical role in prostate tumor progression and its upregulation in mCRPC/NE provides a rationale for assessing the role of ISL1 and its associated protein in treatment resistance.
引用
收藏
页码:2223 / 2231
页数:9
相关论文
共 25 条
[1]   Validation of a 10-gene molecular signature for predicting biochemical recurrence and clinical metastasis in localized prostate cancer [J].
Abou-Ouf, Hatem ;
Alshalalfa, Mohammed ;
Takhar, Mandeep ;
Erho, Nicholas ;
Donnelly, Bryan ;
Davicioni, Elai ;
Karnes, R. Jeffrey ;
Bismar, Tarek A. .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2018, 144 (05) :883-891
[2]   ISL1 expression is not restricted to pancreatic well-differentiated neuroendocrine neoplasms, but is also commonly found in well and poorly differentiated neuroendocrine neoplasms of extrapancreatic origin [J].
Agaimy, Abbas ;
Erlenbach-Wuensch, Katharina ;
Konukiewitz, Bjoern ;
Schmitt, Anja M. ;
Rieker, Ralf J. ;
Vieth, Michael ;
Kiesewetter, Franklin ;
Hartmann, Arndt ;
Zamboni, Giuseppe ;
Perren, Aurel ;
Kloeppel, Guenter .
MODERN PATHOLOGY, 2013, 26 (07) :995-1003
[3]   The Placental Gene PEG10 Promotes Progression of Neuroendocrine Prostate Cancer [J].
Akamatsu, Shusuke ;
Wyatt, Alexander W. ;
Lin, Dong ;
Lysakowski, Summer ;
Zhang, Fan ;
Kim, Soojin ;
Tse, Charan ;
Wang, Kendric ;
Mo, Fan ;
Haegert, Anne ;
Brahmbhatt, Sonal ;
Bell, Robert ;
Adomat, Hans ;
Kawai, Yoshihisa ;
Xue, Hui ;
Dong, Xin ;
Fazli, Ladan ;
Tsai, Harrison ;
Lotan, Tamara L. ;
Kossai, Myriam ;
Mosquera, Juan Miguel ;
Rubin, Mark A. ;
Beltran, Himisha ;
Zoubeidi, Amina ;
Wang, Yuzhuo ;
Gleave, Martin E. ;
Collins, Colin C. .
CELL REPORTS, 2015, 12 (06) :922-936
[4]   MEIS1 and MEIS2 Expression and Prostate Cancer Progression: A Role For HOXB13 Binding Partners in Metastatic Disease [J].
Bhanvadia, Raj R. ;
VanOpstall, Calvin ;
Brechka, Hannah ;
Barashi, Nimrod S. ;
Gillard, Marc ;
McAuley, Erin M. ;
Vasquez, Juan Manuel ;
Paner, Gladell ;
Chan, Wen-Ching ;
Andrade, Jorge ;
De Marzo, Angelo M. ;
Han, Misop ;
Szmulewitz, Russell Z. ;
Vander Griend, Donald J. .
CLINICAL CANCER RESEARCH, 2018, 24 (15) :3668-3680
[5]   Interrogation of ERG gene rearrangements in prostate cancer identifies a prognostic 10-gene signature with relevant implication to patients' clinical outcome [J].
Bismar, Tarek A. ;
Alshalalfa, Mohammed ;
Petersen, Lars F. ;
Teng, Liang Hong ;
Gerke, Travis ;
Bakkar, Ashraf ;
Al-Mami, Amal ;
Liu, Shuhong ;
Dolph, Michael ;
Mucci, Lorelei A. ;
Alhajj, Reda .
BJU INTERNATIONAL, 2014, 113 (02) :309-319
[6]   Cooperative Transcriptional Activation by Klf4, Meis2, and Pbx1 [J].
Bjerke, Glen A. ;
Hyman-Walsh, Cathy ;
Wotton, David .
MOLECULAR AND CELLULAR BIOLOGY, 2011, 31 (18) :3723-3733
[7]   Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart [J].
Cai, CL ;
Liang, XQ ;
Shi, YQ ;
Chu, PH ;
Pfaff, SL ;
Chen, J ;
Evans, S .
DEVELOPMENTAL CELL, 2003, 5 (06) :877-889
[8]   Deregulation of a Hox Protein Regulatory Network Spanning Prostate Cancer Initiation and Progression [J].
Chen, James L. ;
Li, Jianrong ;
Kiriluk, Kyle J. ;
Rosen, Alex M. ;
Paner, Gladell P. ;
Antic, Tatjana ;
Lussier, Yves A. ;
Vander Griend, Donald J. .
CLINICAL CANCER RESEARCH, 2012, 18 (16) :4291-4302
[9]   Discovery and Validation of a Prostate Cancer Genomic Classifier that Predicts Early Metastasis Following Radical Prostatectomy [J].
Erho, Nicholas ;
Crisan, Anamaria ;
Vergara, Ismael A. ;
Mitra, Anirban P. ;
Ghadessi, Mercedeh ;
Buerki, Christine ;
Bergstralh, Eric J. ;
Kollmeyer, Thomas ;
Fink, Stephanie ;
Haddad, Zaid ;
Zimmermann, Benedikt ;
Sierocinski, Thomas ;
Ballman, Karla V. ;
Triche, Timothy J. ;
Black, Peter C. ;
Karnes, R. Jeffrey ;
Klee, George ;
Davicioni, Elai ;
Jenkins, Robert B. .
PLOS ONE, 2013, 8 (06)
[10]   The mutational landscape of lethal castration-resistant prostate cancer [J].
Grasso, Catherine S. ;
Wu, Yi-Mi ;
Robinson, Dan R. ;
Cao, Xuhong ;
Dhanasekaran, Saravana M. ;
Khan, Amjad P. ;
Quist, Michael J. ;
Jing, Xiaojun ;
Lonigro, Robert J. ;
Brenner, J. Chad ;
Asangani, Irfan A. ;
Ateeq, Bushra ;
Chun, Sang Y. ;
Siddiqui, Javed ;
Sam, Lee ;
Anstett, Matt ;
Mehra, Rohit ;
Prensner, John R. ;
Palanisamy, Nallasivam ;
Ryslik, Gregory A. ;
Vandin, Fabio ;
Raphael, Benjamin J. ;
Kunju, Lakshmi P. ;
Rhodes, Daniel R. ;
Pienta, Kenneth J. ;
Chinnaiyan, Arul M. ;
Tomlins, Scott A. .
NATURE, 2012, 487 (7406) :239-243