Oncotarget

Research Papers:

Upregulation of FAM84B during prostate cancer progression

Nicholas Wong, Yan Gu, Anil Kapoor, Xiaozeng Lin, Diane Ojo, Fengxiang Wei, Judy Yan, Jason de Melo, Pierre Major, Geoffrey Wood, Tariq Aziz, Jean-Claude Cutz, Michael Bonert, Arthur J. Patterson and Damu Tang _

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Oncotarget. 2017; 8:19218-19235. https://doi.org/10.18632/oncotarget.15168

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Abstract

Nicholas Wong1,2,3, Yan Gu1,2,3, Anil Kapoor2,4, Xiaozeng Lin1,2,3, Diane Ojo1,2,3, Fengxiang Wei1,2,3,5, Judy Yan1,2,3, Jason de Melo1,2,3, Pierre Major6, Geoffrey Wood7, Tariq Aziz8, Jean-Claude Cutz8, Michael Bonert8, Arthur J. Patterson1,2,3, Damu Tang1,2,3

1Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada

2Father Sean O’Sullivan Research Institute, Hamilton, Ontario, Canada

3The Hamilton Center for Kidney Research, St. Joseph’s Hospital, Hamilton, Ontario, Canada

4Department of Surgery, McMaster University, Hamilton, Ontario, Canada

5The Genetics Laboratory, Longgang District Maternity and Child Healthcare Hospital, Longgang District, Shenzhen, Guangdong, P.R. China

6Division of Medical Oncology, Department of Oncology, McMaster University, Ontario, Canada

7Department of Veterinary Pathology, University of Guelph, Guelph, Ontario, Canada

8Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada

Correspondence to:

Damu Tang, email: [email protected]

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 OncomineTM 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.


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