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Meis proteins as predictive markers of metastatic prostate cancer progression

Login to Access Video or Poster Abstract: MP87-04
Sources of Funding: University of Chicago Pritzker Fellowship Program_x000D_ _x000D_ DOD grant PCRP PC130587, PI: Vander Griend

Introduction

Improvement in prostate cancer (PCa) management requires better understanding of mechanisms of PCa progression. Previous studies identified Meis (myeloid ecotropic viral integration site) as a putative biomarker capable of prognostic prediction in PCa. This study analyzed RNA-sequencing (RNA-seq) of 26 tumors and 90 metastases to identify Meis related genes associated with metastatic progression, and examined the negative predictive value (NPV) of Meis in developing metastatic PCa using tissue microarrays (TMA).

Methods

Annotated TMAs of patients who underwent radical prostatectomy (RP) for PCa were stained for Meis and scored by a single genitourinary pathologist. NPV was calculated for the ability of Meis positivity (+Meis) to predict clinical metastasis, defined as radiographic or pathologic evidence of metastasis. RNA-seq of 26 tumors, and 90 metastases were obtained from publically available data. The 26 tumors were stratified by Meis expression, and pair-wise analysis to the metastases identified genes in low Meis tumors associated with metastatic progression.

Results

A total of 99 patients underwent RP for PCa. There was no difference in age, race, stage, or Gleason grade among +Meis and Meis negative (-Meis) patients. 23% (n= 23) of patients had a +Meis score. 10% (n= 10) of patients demonstrated evidence of clinical metastasis. Of the 76 -Meis patients, 13% (n= 10) developed clinical metastasis; 0 +Meis patients developed metastasis (NPV= 100%). RNA-Seq of Meis low tumors had an expression profile closest to metastatic lesions compared to Meis high tumors. Pair wise analysis of tumors compared to metastases identified 1082 differentially expressed genes (DEG) in Meis low tumors associated with metastatic progression.

Conclusions

+Meis negatively predicted 100% of clinical metastasis in post-RP PCa, supporting its prognostic role in PCa. RNA-Seq identified 1082 DEG associated with Meis low tumors and metastatic progression. Further analysis of these genes can potentially identify novel approaches toward preventing and treating metastatic PCa.

Funding

University of Chicago Pritzker Fellowship Program_x000D_ _x000D_ DOD grant PCRP PC130587, PI: Vander Griend

Authors
Raj Bhanvadia
Erin McAuley
Wen-Ching Chan
Hannah Brechka
Gladell Paner
Donald Vander Griend
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