Amplification of MUC1 in prostate cancer metastasis and CRPC development

This is the authors' abstract. We don't add key points for this paper.

// Nicholas Wong 1, 2, 3 , Pierre Major 4 , Anil Kapoor 2, 5 , Fengxiang Wei 1, 2, 3, 6 , Judy Yan 1, 2, 3 , Tariq Aziz 7 , Mingxing Zheng 8, 9 , Dulitha Jayasekera 1, 2, 3 , Jean-Claude Cutz 7 , Mathilda Jing Chow 1, 2, 3 , Damu Tang 1, 2, 3 1 Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada 2 Father Sean O’Sullivan Research Institute, Hamilton, Ontario, Canada 3 The Hamilton Center for Kidney Research, St. Joseph’s Hospital, Hamilton, Ontario, Canada 4 Division of Medical Oncology, Department of Oncology, McMaster University, Hamilton, Ontario, Canada 5 Department of Surgery, McMaster University, Hamilton, Ontario, Canada 6 The Genetics Laboratory, Longgang District Maternity and Child Healthcare Hospital, Longgang District, Shenzhen, Guangdong, P.R. China 7 Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada 8 Department of Respiratory Medicine, Shenzhen 2nd People’s Hospital, Shenzhen, Guangdong, China 9 Department of Respiratory Disease, The First Affiliated Hospital of Shenzhen University Medical School, Shenzhen, Guangdong, China Correspondence to: Damu Tang, email: damut@mcmaster.ca Keywords: MUC1, prostate cancer, prostate cancer stem cells, metastasis, castration resistant prostate cancer Received: April 16, 2016     Accepted: October 16, 2016     Published: November 04, 2016 ABSTRACT Evidence supports the upregulation of MUC1 in prostate cancer (PC). However, this has not been thoroughly investigated. We report here an association of MUC1 upregulation with PC metastasis and the development of castration resistant PC (CRPC). MUC1 expression was specifically increased in DU145 cell-derived PC stem-like cells (PCSLCs) in comparison to their non-PCSLCs counterparts. While immunohistochemistry staining of 34 primary PCs revealed variability in MUC1 expression, Nanostring technology demonstrated elevated MUC1 mRNA levels in 4 of 7 PCs compared to their normal matched tissues. By analyzing MUC1 mRNA levels and gene copy number (GCN) using the Oncomine TM database, elevations in MUC1 mRNA in 82 metastases versus 280 primary PCs and in MUC1 GCN in 37 metastases over 181 primary tumors were demonstrated. Analysis of genomic datasets within cBioPortal revealed increases in MUC1 GCN in 2% (6/333) of primary PCs, 6% (9/150) of metastatic PCs, and 33% (27/82) of CRPCs; in comparison, the respective increase in androgen receptor (AR) GCN was 1%, 63%, and 56%, revealing a specific increase in MUC1 GCN for CRPC. Furthermore, a 25-gene MUC1 network was amplified in 52% of CRPCs compared to 69% of CRPCs displaying increases in an AR co-regulator group. While genomic alterations in the MUC1 network largely overlap with those in the AR group, 18 CRPCs (66.7% being neuroendocrine PC) showed genomic alterations only in the MUC1 network. Moreover, genomic alterations in the MUC1 network correlated with PC relapse. Collectively, our observations suggest a combination therapy involving MUC1-based immunotherapy and androgen deprivation.