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An m6A-driven prognostic marker panel for renal cell carcinoma based on the first transcriptome-wide m6A-seq

To date, only a single transcriptome-wide m6A sequencing study of clear cell renal cell carcinoma (ccRCC) has been reported, with no validation so far. Herein, by TCGA analysis of the KIRC cohort (n = 530 ccRCC; n = 72 normal), an external expression validation of 35 preidentified m6A targets was pe...

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Hauptverfasser: Waldbillig, Frank (VerfasserIn) , Bormann, Felix (VerfasserIn) , Neuberger, Manuel (VerfasserIn) , Ellinger, Jörg (VerfasserIn) , Erben, Philipp (VerfasserIn) , Kriegmair, Maximilian (VerfasserIn) , Michel, Maurice Stephan (VerfasserIn) , Nuhn, Philipp (VerfasserIn) , Nientiedt, Malin (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 21 February 2023
In: Diagnostics
Year: 2023, Jahrgang: 13, Heft: 5, Pages: 1-11
ISSN:2075-4418
DOI:10.3390/diagnostics13050823
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/diagnostics13050823
Verlag, kostenfrei, Volltext: https://www.mdpi.com/2075-4418/13/5/823
Volltext
Verfasserangaben:Frank Waldbillig, Felix Bormann, Manuel Neuberger, Jörg Ellinger, Philipp Erben, Maximilian C. Kriegmair, Maurice Stephan Michel, Philipp Nuhn and Malin Nientiedt
Beschreibung
Zusammenfassung:To date, only a single transcriptome-wide m6A sequencing study of clear cell renal cell carcinoma (ccRCC) has been reported, with no validation so far. Herein, by TCGA analysis of the KIRC cohort (n = 530 ccRCC; n = 72 normal), an external expression validation of 35 preidentified m6A targets was performed. Further in-depth expression stratification enabled assessment of m6A-driven key targets. Overall survival (OS) analysis and gene set enrichment analyses (GSEA) were conducted to assess their clinical and functional impact on ccRCC. In the hyper-up cluster significant upregulation was confirmed for NDUFA4L2, NXPH4, SAA1, and PLOD2 (40%) and in the hypo-up cluster for FCHSD1 (10%). Significant downregulation was observed for UMOD, ANK3, and CNTFR (27.3%) in the hypo-down cluster and for CHDH (25%) in the hyper-down cluster. In-depth expression stratification showed consistent dysregulation in ccRCC only for 11.67%: NDUFA4L2, NXPH4, and UMOD (NNU-panel). Patients with strong NNU panel dysregulation had significantly poorer OS (p = 0.0075). GSEA identified 13 associated and significantly upregulated gene sets (all p-values < 0.5; FDR < 0.25). External validation of the only available m6A sequencing in ccRCC consistently reduced dysregulated m6A-driven targets on the NNU panel with highly significant effects on OS. Epitranscriptomics are a promising target for developing novel therapies and for identifying prognostic markers for daily clinical practice.
Beschreibung:Gesehen am 14.04.2023
Beschreibung:Online Resource
ISSN:2075-4418
DOI:10.3390/diagnostics13050823

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