The role of SPINK1 in ETS rearrangement-negative prostate cancers.
Abstact
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.
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Authors
- Al-Ahmadie H
- Andrén O
- Bjartell AS
- Cao Q
- Cao X
- Chinnaiyan AM
- Demichelis F
- Eastham JA
- Eggener SE
- Fall K
- Fine SW
- Gerald WL
- Helgeson BE
- Hotakainen K
- Johnson L
- Kantoff PW
- Laxman B
- Lilja H
- Mehra R
- Morris DS
- Perner S
- Reuter VE
- Rhodes DR
- Rubin MA
- Scardino PT
- Shah RB
- Stenman UH
- Tomlins SA
- Tsodikov A
- Varambally S
- Wei JT
- Yu J