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- W3021880981 abstract "INTRODUCTION AND OBJECTIVE: Since prostate cancer (PCa) is considered to be unaffected by immunotherapy being a “cold” tumor, research on novel targets may give insight on how to make it susceptible. The TAM tyrosine kinase MERTK is an interesting target, since it both suppresses immune reaction in the tumor microenvironment and is also expressed directly by cancer cells. We analyzed its immunohistochemical (IHC) expression and how it correlates to the prognostic features of PCa. Moreover, we performed differential gene expression and pathway analysis on RNA-Seq data from PCa cases, to obtain information about the single genes and the intracellular pathways that are modulated by MERTK. METHODS: We stained tissue microarrays of 532 PCa cases for MERTK. Cases comprised localized PCa, and metastases with morphology of adenocarcinoma or neuroendocrine adenocarcinoma (NEPC). We used a H-score for IHC and collected the Gleason scores. We also studied RNA-Seq data from a 217 PCa cohort by performing differential expression analysis and pathway analysis with the R packages “DESeq” and “gage”. RESULTS: IHC analysis suggested that MERTK tends to be less expressed in in NEPC and metastases with respect to localized PCa. No correlation with Gleason score was noted. Differential expression analysis revealed that the most significantly down-regulated genes included a group encoding for proteins regulating mitotic spindle and chromosomal stability. Pathway analysis found five intracellular pathways that were up-regulated in the high-MERTK group: three of these, – the focal adhesion pathway, the vascular smooth muscle pathway, and the drug metabolism/cytochrome p450 pathway – have a function that is coherent with known effects of MERTK. CONCLUSIONS: The relationship between MERTK expression and prognosis in prostate cancer is not straightforward. In particular, negative correlation of high immunohistochemical expression with NEPC and metastases is interesting. We also concluded that the intracellular pathways through which MERTK modulates cell mobility and drug resistance in PCa are, respectively, the RhoA pathway and the cytochrome pathway. Source of Funding: Ospedale San Raffaele pathology department and Weill-Cornell pathology department." @default.
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- W3021880981 date "2020-04-01" @default.
- W3021880981 modified "2023-10-14" @default.
- W3021880981 title "MP09-17 A POTENTIALLY NOVEL IMMUNOTHERAPY TARGET IN PROSTATE CANCER" @default.
- W3021880981 doi "https://doi.org/10.1097/ju.0000000000000829.017" @default.
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