Upregulation of FAM84B during prostate cancer progression

// Nicholas Wong 1, 2, 3 , Yan Gu 1, 2, 3 , Anil Kapoor 2, 4 , Xiaozeng Lin 1, 2, 3 , Diane Ojo 1, 2, 3 , Fengxiang Wei 1, 2, 3, 5 , Judy Yan 1, 2, 3 , Jason de Melo 1, 2, 3 , Pierre Major 6 , Geoffrey Wood 7 , Tariq Aziz 8 , Jean-Claude Cutz 8 , Michael Bonert 8 , Arthur J. Patterson 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 Department of Surgery, McMaster University, Hamilton, Ontario, Canada 5 The Genetics Laboratory, Longgang District Maternity and Child Healthcare Hospital, Longgang District, Shenzhen, Guangdong, P.R. China 6 Division of Medical Oncology, Department of Oncology, McMaster University, Ontario, Canada 7 Department of Veterinary Pathology, University of Guelph, Guelph, Ontario, Canada 8 Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada Correspondence to: Damu Tang, email: damut@mcmaster.ca Keywords: FAM84B, prostate cancer, prostate cancer stem cells, metastasis, castration resistant prostate cancer Received: May 27, 2016      Accepted: January 23, 2017      Published: February 07, 2017 ABSTRACT Although the FAM84B gene lies within chromosome 8q24, a locus frequently altered in prostate cancer (PC), its alteration during prostate tumorigenesis has not been well studied. We report here FAM84B upregulation in DU145 cell-derived prostate cancer stem-like cells (PCSLCs) and DU145 cell-produced lung metastases compared to subcutaneous xenograft tumors. FAM84B protein was detected in bone metastases and primary PCs. Nanostring examination of 7 pairs of tumor adjacent normal and PC tissues revealed elevations in FAM84B mRNA levels in all carcinomas. Furthermore, through analysis of FAM84B expression using large datasets within the Gene Expression Omnibus and Oncomine TM database, we demonstrate significant increases in FAM84B mRNA in 343 primary PCs versus 181 normal tissues, and elevations in the FAM84B gene copy number (GCN) in 171 primary PCs versus 61 normal tissues. While FAM84B was not detected at higher levels via immunohistochemistry in high grade (Gleason score/GS 8-10) tumors compared to GS6-7 PCs, analyses of FAM84B mRNA and GCN using datasets within the cBioPortal database demonstrated FAM84B upregulation in 12% (67/549) of primary PCs and 18% (73/412) of metastatic castration resistant PCs (mCRPCs), and GCN increases in 4.8% (26/546) of primary PCs and 26% (121/467) of mCRPCs, revealing an association of the aforementioned changes with CRPC development. Of note, an increase in FAM84B expression was observed in xenograft CRPCs produced by LNCaP cells. Furthermore, FAM84B upregulation and GCN increases correlate with decreases in disease free survival and overall survival. Collectively, we demonstrate a novel association of FAM84B with PC tumorigenesis and CRPC progression.