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An m6A-Driven Prognostic Marker Panel for Renal Cell Carcinoma Based on the First Transcriptome-Wide m6A-seq
oleh: Frank Waldbillig, Felix Bormann, Manuel Neuberger, Jörg Ellinger, Philipp Erben, Maximilian C. Kriegmair, Maurice Stephan Michel, Philipp Nuhn, Malin Nientiedt
Format: | Article |
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Diterbitkan: | MDPI AG 2023-02-01 |
Deskripsi
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 (<i>n</i> = 530 ccRCC; <i>n</i> = 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 (<i>p</i> = 0.0075). GSEA identified 13 associated and significantly upregulated gene sets (all <i>p</i>-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.