title: Endosomal gene expression: a new indicator for prostate cancer patient prognosis?
abstract: Prostate cancer continues to be a major cause of morbidity and mortality in men, but a method for accurate prognosis in these patients is yet to be developed. The recent discovery of altered endosomal biogenesis in prostate cancer has identified a fundamental change in the cell biology of this cancer, which holds great promise for the identification of novel biomarkers that can predict disease outcomes. Here we have identified significantly altered expression of endosomal genes in prostate cancer compared to non-malignant tissue in mRNA microarrays and confirmed these findings by qRT-PCR on fresh-frozen tissue. Importantly, we identified endosomal gene expression patterns that were predictive of patient outcomes. Two endosomal tri-gene signatures were identified from a previously published microarray cohort and had a significant capacity to stratify patient outcomes. The expression of APPL1, RAB5A, EEA1, PDCD6IP, NOX4 and SORT1 were altered in malignant patient tissue, when compared to indolent and normal prostate tissue. These findings support the initiation of a case-control study using larger cohorts of prostate tissue, with documented patient outcomes, to determine if different combinations of these new biomarkers can accurately predict disease status and clinical progression in prostate cancer patients.
authors.affiliation: Mechanisms in Cell Biology and Disease Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia.
authors.forename: Ian R D
authors.initials: IR
authors.lastname: Johnson
authors.affiliation: Mechanisms in Cell Biology and Disease Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Parkinson-Lawrence
authors.affiliation: Department of Pathology, Coombe Women and Infants University Hospital, Dublin, Ireland.|Department of Histopathology, Trinity College Dublin, Dublin, Ireland.
authors.forename: Helen
authors.initials: H
authors.lastname: Keegan
authors.affiliation: Department of Histopathology, Trinity College Dublin, Dublin, Ireland.
authors.forename: Cathy D
authors.initials: CD
authors.lastname: Spillane
authors.affiliation: Department of Pathology, Coombe Women and Infants University Hospital, Dublin, Ireland.
authors.forename: Jacqui
authors.initials: J
authors.lastname: Barry-O'Crowley
authors.affiliation: UCD School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: William R
authors.initials: WR
authors.lastname: Watson
authors.affiliation: Infection and Immunity Program, Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, VIC, Australia.
authors.forename: Stavros
authors.initials: S
authors.lastname: Selemidis
authors.affiliation: Prostate Cancer Research Group, School of Medicine and Freemasons Centre for Men's Health, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Butler
authors.affiliation: Department of Pathology, Coombe Women and Infants University Hospital, Dublin, Ireland.|Department of Histopathology, Trinity College Dublin, Dublin, Ireland.
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Leary
authors.affiliation: Mechanisms in Cell Biology and Disease Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia.
authors.forename: Doug A
authors.initials: DA
authors.lastname: Brooks
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D015331:Cohort Studies; D018450:Disease Progression; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics; D011992:Endosomes / Q000378:metabolism*; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D033921:Vesicular Transport Proteins / Q000235:genetics; D020696:rab5 GTP-Binding Proteins / Q000235:genetics; D000099183:Sortilin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; D020696:rab5 GTP-Binding Proteins; D000099183:Sortilin; C464801:APPL1 protein, human; C117020:PDCD6IP protein, human; C093846:early endosome antigen 1; C498910:NOX4 protein, human; C427755:RAB5C protein, human
keywords: biomarkers; endosomal gene expression; mRNA; prognosis; prostate cancer