title: Upregulation of FAM84B during prostate cancer progression.
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.
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada.|The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wong
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada.|The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada.|Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Anil
authors.initials: A
authors.lastname: Kapoor
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada.|The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors.forename: Xiaozeng
authors.initials: X
authors.lastname: Lin
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada.|The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors.forename: Diane
authors.initials: D
authors.lastname: Ojo
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada.|The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.|The Genetics Laboratory, Longgang District Maternity and Child Healthcare Hospital, Longgang District, Shenzhen, Guangdong, P.R. China.
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Wei
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada.|The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors.forename: Judy
authors.initials: J
authors.lastname: Yan
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada.|The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: de Melo
authors.affiliation: Division of Medical Oncology, Department of Oncology, McMaster University, Ontario, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Major
authors.affiliation: Department of Veterinary Pathology, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Wood
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Tariq
authors.initials: T
authors.lastname: Aziz
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Cutz
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Bonert
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada.|The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Patterson
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada.|The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors.forename: Damu
authors.initials: D
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C585865:LRATD2 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins
keywords: FAM84B; castration resistant prostate cancer; metastasis; prostate cancer; prostate cancer stem cells