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Title: Hypertonicity-affected genes are differentially expressed in clear cell renal cell carcinoma and correlate with cancer-specific survival
Author(s): Kandabarau, Siarhei
Leiz, Janna
Krohn, Knut
Winter, Stefan
Bedke, JensLook up in the Integrated Authority File of the German National Library
Schwab, Matthias
Schaeffeler, Elke
Edemir, BayramLook up in the Integrated Authority File of the German National Library
Issue Date: 2020
Type: Article
Language: English
Abstract: The heterogeneity of renal cell carcinoma (RCC) subtypes reflects the cell type of origin in the nephron, with consequences for therapy and prognosis. The transcriptional cues that determine segment-specific gene expression patterns are poorly understood. We recently showed that hypertonicity in the renal medulla regulates nephron-specific gene expression. Here, we analyzed a set of 223 genes, which were identified in the present study by RNA-Seq to be differentially expressed by hypertonicity, for the prediction of cancer-specific survival (CSS). Cluster analyses of these genes showed discrimination between tumor and non-tumor samples of clear cell RCC (ccRCC). Refinement of this gene signature to a four-gene score (OSM score) through statistical analyses enabled prediction of CSS in ccRCC patients of The Cancer Genome Atlas (TCGA) (n = 436) in univariate (HR = 4.1; 95% CI: 2.78−6.07; p = 4.39 × 10−13), and multivariate analyses including primary tumor (T); regional lymph node (N); distant metastasis (M); grading (G)(p = 2.3 × 10−5). The OSM score could be validated in an independent ccRCC study (n = 52) in univariate (HR = 1.29; 95% CI = 1.05–1.59; p = 0.011) and multivariate analyses (p = 0.016). Cell culture experiments using RCC cell lines demonstrated that the expression of the tumor suppressor ELF5 could be restored by hypertonicity. The innovation of our novel gene signature is that these genes are physiologically regulated only by hypertonicity, thereby providing the possibility to be targeted for therapy.
Open Access: Open access publication
License: (CC BY 4.0) Creative Commons Attribution 4.0(CC BY 4.0) Creative Commons Attribution 4.0
Sponsor/Funder: Publikationsfond MLU
Journal Title: Cancers
Publisher: MDPI
Publisher Place: Basel
Volume: 12
Issue: 1
Original Publication: 10.3390/cancers12010006
Appears in Collections:Open Access Publikationen der MLU

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