Endosomal gene expression: a new indicator for prostate cancer patient prognosis?
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Ian R.D. Johnson1, Emma J. Parkinson-Lawrence1, Helen Keegan2,3, Cathy D. Spillane3, Jacqui Barry-O’Crowley2, William R. Watson4, Stavros Selemidis5, Lisa M. Butler6, John J. O’Leary2,3 and Doug A. Brooks1
1 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
2 Department of Pathology, Coombe Women and Infants University Hospital, Dublin, Ireland
3 Department of Histopathology, Trinity College Dublin, Dublin, Ireland
4 UCD School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
5 Infection and Immunity Program, Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, VIC, Australia
6 Prostate Cancer Research Group, School of Medicine and Freemasons Centre for Men’s Health, University of Adelaide, Adelaide, SA, Australia
Doug A. Brooks, email:
Keywords: prostate cancer, biomarkers, prognosis, endosomal gene expression, mRNA
Received: September 23, 2015 Accepted: September 28, 2015 Published: October 14, 2015
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.
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