Endosomal gene expression: a new indicator for prostate cancer patient prognosis?

被引:34
作者
Johnson, Ian R. D. [1 ]
Parkinson-Lawrence, Emma J. [1 ]
Keegan, Helen [2 ,3 ]
Spillane, Cathy D. [3 ]
Barry-O'Crowley, Jacqui [2 ]
Watson, William R. [4 ]
Selemidis, Stavros [5 ]
Butler, Lisa M. [6 ,7 ]
O'Leary, John J. [2 ,3 ]
Brooks, Doug A. [1 ]
机构
[1] Univ S Australia, Sansom Inst Hlth Res, Sch Pharm & Med Sci, Mech Cell Biol & Dis Res Grp, Adelaide, SA 5001, Australia
[2] Coombe Women & Infants Univ Hosp, Dept Pathol, Dublin, Ireland
[3] Univ Dublin Trinity Coll, Dept Histopathol, Dublin 2, Ireland
[4] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, UCD Sch Med & Med Sci, Dublin 2, Ireland
[5] Monash Univ, Dept Pharmacol, Biomed Discovery Inst, Infect & Immun Program, Clayton, Vic 3168, Australia
[6] Univ Adelaide, Sch Med, Prostate Canc Res Grp, Adelaide, SA, Australia
[7] Univ Adelaide, Freemasons Ctr Mens Hlth, Adelaide, SA, Australia
基金
澳大利亚研究理事会; 澳大利亚国家健康与医学研究理事会;
关键词
prostate cancer; biomarkers; prognosis; endosomal gene expression; mRNA; ACID CERAMIDASE; BIOMARKERS; PERFORMANCE; STATISTICS; SIGNATURES; SURVIVAL; ANTIGEN; TISSUE; PCA3; RNA;
D O I
10.18632/oncotarget.6114
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:37919 / 37929
页数:11
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