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.
Keywords:
biomarkers; endosomal gene expression; mRNA; prognosis; prostate cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Vesicular Transport / genetics
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Biomarkers, Tumor / genetics*
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Calcium-Binding Proteins / genetics
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Cell Cycle Proteins / genetics
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Cohort Studies
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Disease Progression
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Endosomal Sorting Complexes Required for Transport / genetics
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Endosomes / metabolism*
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Follow-Up Studies
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Gene Expression Profiling
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Humans
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Male
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NADPH Oxidase 4
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NADPH Oxidases / genetics
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Neoplasm Grading
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Neoplasm Metastasis
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Neoplasm Recurrence, Local / genetics*
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Neoplasm Recurrence, Local / mortality
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Neoplasm Recurrence, Local / pathology
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Prognosis
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Prostatic Intraepithelial Neoplasia / genetics*
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Prostatic Intraepithelial Neoplasia / mortality
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Prostatic Intraepithelial Neoplasia / pathology
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Prostatic Neoplasms / genetics*
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Prostatic Neoplasms / mortality
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Prostatic Neoplasms / pathology
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Survival Rate
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Vesicular Transport Proteins / genetics
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rab5 GTP-Binding Proteins / genetics
Substances
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APPL1 protein, human
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Biomarkers, Tumor
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Calcium-Binding Proteins
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Cell Cycle Proteins
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Endosomal Sorting Complexes Required for Transport
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PDCD6IP protein, human
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RNA, Messenger
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Vesicular Transport Proteins
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early endosome antigen 1
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NADPH Oxidase 4
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NADPH Oxidases
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NOX4 protein, human
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RAB5C protein, human
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rab5 GTP-Binding Proteins
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sortilin