The role of SPINK1 in ETS rearrangement-negative prostate cancers.
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.
Tomlins
Scott A
SA
Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Rhodes
Daniel R
DR
Yu
Jianjun
J
Varambally
Sooryanarayana
S
Mehra
Rohit
R
Perner
Sven
S
Demichelis
Francesca
F
Helgeson
Beth E
BE
Laxman
Bharathi
B
Morris
David S
DS
Cao
Qi
Q
Cao
Xuhong
X
Andrén
Ove
O
Fall
Katja
K
Johnson
Laura
L
Wei
John T
JT
Shah
Rajal B
RB
Al-Ahmadie
Hikmat
H
Eastham
James A
JA
Eggener
Scott E
SE
Fine
Samson W
SW
Hotakainen
Kristina
K
Stenman
Ulf-Håkan
UH
Tsodikov
Alex
A
Gerald
William L
WL
Lilja
Hans
H
Reuter
Victor E
VE
Kantoff
Phillip W
PW
Scardino
Peter T
PT
Rubin
Mark A
MA
Bjartell
Anders S
AS
Chinnaiyan
Arul M
AM
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D045744:Cell Line, Tumor; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005060:Europe; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012008:Recurrence; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071230:Transcriptional Regulator ERG; D014162:Transfection; D016896:Treatment Outcome; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014481:United States
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; C095239:ETV1 protein, human; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C486642:SPINK1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic