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Cancer Cell International
Published in: Cancer Cell International 1/2020

01-12-2020 | Kidney Cancer | Primary research

Identification of a m6A RNA methylation regulators-based signature for predicting the prognosis of clear cell renal carcinoma

Authors: Jing Chen, Kun Yu, Guansheng Zhong, Wei Shen

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

The mortality rate of clear cell renal cell carcinoma (ccRCC) remains high. The aim of this study was to identify novel prognostic biomarkers by using m6A RNA methylation regulators capable of improving the risk-stratification criteria of survival for ccRCC patients.

Methods

The gene expression data of 16 m6A methylation regulators and its relevant clinical information were extracted from The Cancer Genome Atlas (TCGA) database. The expression pattern of these m6A methylation regulators were evaluated. Consensus clustering analysis was conducted to identify clusters of ccRCC patients with different prognosis. Univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were performed to construct multiple-gene risk signature. A survival analysis was carried out to determine the independent prognostic significance of the signature.

Results

Five m6A-related genes (ZC3H13, METTL14, YTHDF2, YTHDF3 and HNRNPA2B1) showed significantly downregulated in tumor tissue, while seven regulators (YTHDC2, FTO, WTAP, METTL3, ALKBH5, RBM15 and KIAA1429) was remarkably upregulated in ccRCC. Consensus clustering analysis identified two clusters of ccRCC with significant differences in overall survival (OS) and tumor stage between them. We also constructed a two-gene signature, METTL3 and METTL14, serving as an independent prognostic indicator for distinguishing ccRCC patients with different prognosis both in training, validation and our own clinical datasets. The receiver operator characteristic (ROC) curve indicated the area under the curve (AUC) in these three datasets were 0.721, 0.684 and 0.828, respectively, demonstrated that the prognostic signature had a good prediction efficiency.

Conclusions

m6A methylation regulators exert as potential biomarkers for prognostic stratification of ccRCC patients and may assist clinicians achieving individualized treatment for this patient population.
Appendix
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Metadata
Title
Identification of a m6A RNA methylation regulators-based signature for predicting the prognosis of clear cell renal carcinoma
Authors
Jing Chen
Kun Yu
Guansheng Zhong
Wei Shen
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01238-3

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