Abstract
ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers ( approximately 10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.
Publication types
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Meta-Analysis
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Multicenter Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism*
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Biomarkers, Tumor / urine
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Carrier Proteins / urine
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Cell Line, Tumor
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Cohort Studies
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Europe
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Gene Expression Profiling / methods
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Gene Expression Regulation, Neoplastic*
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Gene Fusion
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Gene Rearrangement*
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Humans
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Immunohistochemistry
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Male
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Neoplasm Invasiveness
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Oligonucleotide Array Sequence Analysis
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Prostatectomy
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / metabolism*
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Prostatic Neoplasms / pathology
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Prostatic Neoplasms / surgery
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Proto-Oncogene Proteins c-ets / genetics*
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RNA Interference
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RNA, Messenger / metabolism
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RNA, Small Interfering / metabolism
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Recurrence
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Reproducibility of Results
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Risk Assessment
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Risk Factors
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Tissue Array Analysis
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcriptional Regulator ERG
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Transfection
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Treatment Outcome
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Trypsin Inhibitor, Kazal Pancreatic
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United States
Substances
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Biomarkers, Tumor
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Carrier Proteins
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DNA-Binding Proteins
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ERG protein, human
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ETV1 protein, human
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Proto-Oncogene Proteins c-ets
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RNA, Messenger
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RNA, Small Interfering
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SPINK1 protein, human
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Trans-Activators
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Transcription Factors
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Transcriptional Regulator ERG
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Trypsin Inhibitor, Kazal Pancreatic