Prognostic Value of YTHDF2 in Clear Cell Renal Cell Carcinoma
m6A, the main form of mRNA modification, participates in regulating multiple normal and pathological biological events, especially in tumorigenesis. However, there is little known about the association of m6A-related genes with prognosis of clear cell renal cell cancer (ccRCC). Therefore, the progno...
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doaj-2e0c26cd97b540188ffb4e6de51c65d42020-11-25T03:35:01ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-09-011010.3389/fonc.2020.01566548164Prognostic Value of YTHDF2 in Clear Cell Renal Cell CarcinomaZhongyi Mu0Dan Dong1Mingli Sun2Liwen Li3Ning Wei4Ning Wei5Bin Hu6Department of Urology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, ChinaDepartment of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, ChinaSchool of Kinesiology, Shenyang Sport University, Shenyang, ChinaDepartment of Biostatistics, Fairbanks School of Public Health, Indiana University, Indianapolis, IN, United StatesDivision of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesCancer Therapeutics Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Urology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Chinam6A, the main form of mRNA modification, participates in regulating multiple normal and pathological biological events, especially in tumorigenesis. However, there is little known about the association of m6A-related genes with prognosis of clear cell renal cell cancer (ccRCC). Therefore, the prognostic value of m6A-related genes was investigated using Kaplan–Meier curves of overall survival (OS) with the log-rank test and Cox regression analysis. The differential expression of YTHDF2 mRNA in ccRCC and tumor-adjacent normal tissues and associated with clinicopathological characteristics was also analyzed. The alteration of cancer signaling pathways was screened by Gene Set Enrichment Analysis (GSEA). Univariate analysis showed that 15 m6A-related genes (including YTHDF2) were closely related to prognosis. Multivariate analysis further confirmed that YTHDF2 could serve as an independent prognostic factor for the OS of ccRCC patients (P < 0.001). Low-level expression of YTHDF2 had poor prognosis in ccRCC patients with lower tumor–node–metastasis (TNM) stage, age > 61, non-distant metastasis, non-lymph node metastasis, female gender, and higher histological grade (P < 0.05). Moreover, YTHDF2 expression in ccRCC tissues (N = 529) is significantly lower than that of tumor-adjacent normal tissues (N = 72, P = 0.0086). Furthermore, GSEA demonstrated that AKT/mTOR/GSK3 pathway, EIF4 pathway, CHREBP2 pathway, MET pathway, NFAT pathway, FAS pathway, EDG1 pathway, and CTCF pathway are altered in tumors with high YTHDF2 expression. Taken together, our results demonstrated that YTHDF2 (an m6A-related gene) could serve as a potential prognostic biomarker of ccRCC, and targeting epigenetic modification may be a novel therapeutic strategy for the treatment of ccRCC.https://www.frontiersin.org/article/10.3389/fonc.2020.01566/fullm6A-related genesThe Cancer Genome AtlasprognosisYTHDF2clear cell renal cell cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhongyi Mu Dan Dong Mingli Sun Liwen Li Ning Wei Ning Wei Bin Hu |
spellingShingle |
Zhongyi Mu Dan Dong Mingli Sun Liwen Li Ning Wei Ning Wei Bin Hu Prognostic Value of YTHDF2 in Clear Cell Renal Cell Carcinoma Frontiers in Oncology m6A-related genes The Cancer Genome Atlas prognosis YTHDF2 clear cell renal cell cancer |
author_facet |
Zhongyi Mu Dan Dong Mingli Sun Liwen Li Ning Wei Ning Wei Bin Hu |
author_sort |
Zhongyi Mu |
title |
Prognostic Value of YTHDF2 in Clear Cell Renal Cell Carcinoma |
title_short |
Prognostic Value of YTHDF2 in Clear Cell Renal Cell Carcinoma |
title_full |
Prognostic Value of YTHDF2 in Clear Cell Renal Cell Carcinoma |
title_fullStr |
Prognostic Value of YTHDF2 in Clear Cell Renal Cell Carcinoma |
title_full_unstemmed |
Prognostic Value of YTHDF2 in Clear Cell Renal Cell Carcinoma |
title_sort |
prognostic value of ythdf2 in clear cell renal cell carcinoma |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2020-09-01 |
description |
m6A, the main form of mRNA modification, participates in regulating multiple normal and pathological biological events, especially in tumorigenesis. However, there is little known about the association of m6A-related genes with prognosis of clear cell renal cell cancer (ccRCC). Therefore, the prognostic value of m6A-related genes was investigated using Kaplan–Meier curves of overall survival (OS) with the log-rank test and Cox regression analysis. The differential expression of YTHDF2 mRNA in ccRCC and tumor-adjacent normal tissues and associated with clinicopathological characteristics was also analyzed. The alteration of cancer signaling pathways was screened by Gene Set Enrichment Analysis (GSEA). Univariate analysis showed that 15 m6A-related genes (including YTHDF2) were closely related to prognosis. Multivariate analysis further confirmed that YTHDF2 could serve as an independent prognostic factor for the OS of ccRCC patients (P < 0.001). Low-level expression of YTHDF2 had poor prognosis in ccRCC patients with lower tumor–node–metastasis (TNM) stage, age > 61, non-distant metastasis, non-lymph node metastasis, female gender, and higher histological grade (P < 0.05). Moreover, YTHDF2 expression in ccRCC tissues (N = 529) is significantly lower than that of tumor-adjacent normal tissues (N = 72, P = 0.0086). Furthermore, GSEA demonstrated that AKT/mTOR/GSK3 pathway, EIF4 pathway, CHREBP2 pathway, MET pathway, NFAT pathway, FAS pathway, EDG1 pathway, and CTCF pathway are altered in tumors with high YTHDF2 expression. Taken together, our results demonstrated that YTHDF2 (an m6A-related gene) could serve as a potential prognostic biomarker of ccRCC, and targeting epigenetic modification may be a novel therapeutic strategy for the treatment of ccRCC. |
topic |
m6A-related genes The Cancer Genome Atlas prognosis YTHDF2 clear cell renal cell cancer |
url |
https://www.frontiersin.org/article/10.3389/fonc.2020.01566/full |
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