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

• Verfasst von: Waldbillig, Frank [VerfasserIn]
• Verfasst von: Bormann, Felix [VerfasserIn]
• Verfasst von: Neuberger, Manuel [VerfasserIn]
• Verfasst von: Ellinger, Jörg [VerfasserIn]
• Verfasst von: Erben, Philipp [VerfasserIn]
• Verfasst von: Kriegmair, Maximilian [VerfasserIn]
• Verfasst von: Michel, Maurice Stephan [VerfasserIn]
• Verfasst von: Nuhn, Philipp [VerfasserIn]
• Verfasst von: Nientiedt, Malin [VerfasserIn]
• Titel: An m6A-driven prognostic marker panel for renal cell carcinoma based on the first transcriptome-wide m6A-seq
• Verf.angabe: Frank Waldbillig, Felix Bormann, Manuel Neuberger, Jörg Ellinger, Philipp Erben, Maximilian C. Kriegmair, Maurice Stephan Michel, Philipp Nuhn and Malin Nientiedt
• E-Jahr: 2023
• Jahr: 21 February 2023
• Umfang: 11 S.
• Fussnoten: Gesehen am 14.04.2023
• Titel Quelle: Enthalten in: Diagnostics
• Ort Quelle: Basel : MDPI, 2011
• Jahr Quelle: 2023
• Band/Heft Quelle: 13(2023), 5, Artikel-ID 823, Seite 1-11
• ISSN Quelle: 2075-4418
• DOI: doi:10.3390/diagnostics13050823
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: <i>N</i>⁶-methyladenosine (m⁶A)
• Sach-SW: epitranscriptomics
• Sach-SW: kidney cancer
• Sach-SW: m6A-reader
• Sach-SW: MeRip-seq
• Sach-SW: METTL3
• Sach-SW: uromodulin
• K10plus-PPN: 1842671650

Abstract

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.