Abstract
BackgroundSNW1 is a nuclear receptor co-activator involved in splicing and transcription control, including androgen receptor signaling. Overexpression of SNW1 has been linked to adverse prognosis in different cancer types, but studies on the role of SNW1 in prostate cancer are lacking.MethodsUsing immunohistochemistry, we analyzed SNW1 expression in 10,310 prostate cancers in a tissue microarray (TMA) with attached clinical and molecular data.ResultsThe comparison with normal prostate tissue revealed an up regulation of SNW1 in a subset of cancer samples. SNW1 staining was considered weak in 31.5%, moderate in 37.7% and strong in 14% of cancers. Strong SNW1 expression was markedly more frequent in prostate cancers harboring the TMPRSS2:ERG fusion (24%) than in ERG negative cancers (7%, p < 0.0001). Significant associations with Gleason grade, stage, nodal status and early biochemical recurrence were observed in the ERG negative and positive subset. Multivariable modeling revealed that the prognostic value of SNW1 up regulation was independent from the established preoperative histopathological and clinical parameters.ConclusionThese results demonstrate that SNW1 overexpression is an independent prognostic marker in prostate cancer with potential clinical utility.
Highlights
SNW domain-containing protein 1 (SNW1) is a nuclear receptor co-activator involved in splicing and transcription control, including androgen receptor signaling
Association with TMPRSS2:ERG fusion status and ERG protein expression To evaluate whether SNW1 expression is associated with ERG status in prostate cancers, we used data from previous studies
SNW1 expression was strongly linked to TMPRSS2:ERG rearrangement and ERG expression in our set of prostate cancers
Summary
SNW1 is a nuclear receptor co-activator involved in splicing and transcription control, including androgen receptor signaling. SNW domain-containing protein 1 (SNW1) alias SKI-interacting protein 1 (SKIP1) is a multifunctional protein implicated in the regulation of several genes and pathways connected to cell growth and homeostasis. It acts either by direct protein interactions, by mRNA splicing regulation, or by transcriptional control. SNW1 is an important co-regulator for nuclear receptors [7] including vitamin D receptor [8], progesterone and Höflmayer et al Diagnostic Pathology (2019) 14:33 androgen receptor [9] Given these numerous interactions with pathways relevant in cancer, it is not surprising that SNW1 can be up regulated in many cancer types. Studies investigating the potential prognostic impact of SNW1 in clinical prostate cancer samples are currently missing
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