Loss of cadherin related family member 5 (CDHR5) expression in clear cell renal cell carcinoma is a prognostic marker of disease progression
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Felix Marius Bläsius1,*, Sebastian Meller1,*, Carsten Stephan2, Klaus Jung3, Jörg Ellinger4, Michael O. Glocker5, Hans-Jürgen Thiesen5, Yuri Tolkach1,** and Glen Kristiansen1,**
1Institute of Pathology, University Hospital Bonn, Bonn, Germany
2 Clinic of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany
3Berlin Institute for Urologic Research, Robert-Koch Platz 7, Berlin, Germany
4Clinic of Urology, University Hospital Bonn, Bonn, Germany
5Proteome Center Rostock, University of Rostock, Rostock, Germany
*Shared first authors
**Shared senior authors
Glen Kristiansen, email: [email protected]
Keywords: CDHR5, renal cell carcinoma, immunohistochemistry, prognostic marker
Received: March 01, 2017 Accepted: July 29, 2017 Published: August 24, 2017
Reduced expression of Cadherin-Related Family Member 5 (CDHR5) was recently found implied in carcinogenesis of colon cancer, but its role in other tumors is unknown. We aimed to analyze the expression of CDHR5 in different subtypes of renal cell carcinoma. CDHR5 expression was immunohistochemically examined using tissue micro arrays (TMAs) covering 279 patients with primary renal cell carcinoma. Additionally, expression data from the TCGA (The Cancer Genome Atlas) of an independent cohort of 489 clear-cell RCC cases was evaluated. CDHR5 protein expression was found in 74.9% of cases, with higher levels seen in clear cell and papillary RCC. In the univariate analysis CDHR5 expression was significantly associated with a longer overall survival of RCC patients at the protein (p = 0.026, HR = 0.56) and transcript levels (TCGA-cohort: p = 0.0002, HR = 0.55). Importantly, differences in survival times were confirmed independently in multivariate analyses in a model with common clinicopathological variables at the transcript level (p = 0.0097, HR = 0.65). Investigation of the putative functional role of CDHR5 using TCGA data and Enrichment analysis for Gene Ontology and Pathways revealed associations with many metabolic and some tumor growth-associated processes and pathways. CDHR5 expression appears to be a promising and new independent prognostic biomarker in renal cell carcinoma.
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