The N6-Methyladenosine Methylation Gene YTHDFI Reveals a Potential Diagnostic Role for Gastric Cancer

Purpose: Gastric cancer (GC) is aggressive cancer with a high mortality rate worldwide. N6-methyladenosine (m6A) RNA methylation is related to tumorigenesis, which is dynamically regulated by m6A modulators ("writer," "eraser," and "reader"). We conducted a comprehensiv...

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Bibliographic Details
Published in:Cancer management and research 2020-11, Vol.12, p.11953
Main Authors: Liu, Tong, Yang, Sheng, Cheng, Yan-Ping, Kong, Xiao-Ling, Du, Dan-Dan, Wang, Xian, Bai, Yun-Fei, Yin, Li-Hong, Pu, Yue-Pu, Liang, Ge-Yu
Format: Article
Language:English
Subjects:
Cancer
China
Genes
Genetic aspects
Health aspects
Mediation
Medical research
Medicine, Experimental
Methylation
Methyltransferases
Mortality
RNA
Stomach cancer
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Summary:Purpose: Gastric cancer (GC) is aggressive cancer with a high mortality rate worldwide. N6-methyladenosine (m6A) RNA methylation is related to tumorigenesis, which is dynamically regulated by m6A modulators ("writer," "eraser," and "reader"). We conducted a comprehensive analysis of the m6A genes of GC patients in TCGA datasets to identify the potential diagnostic biomarkers. Materials and Methods: We analyzed the expression profile of m6A genes in the TCGA cohort and constructed a diagnostic-m6A-score (DMS) by the LASSO-logistic model. In addition, by consensus cluster analysis, we identified two different subgroups of GC risk individuals by the expression profile of m6A modulators, revealing that YTHDFl's expression variation profile in GC diagnosis. We also performed RT-qPCR and WB verification in 17 pairs of GC specimens and paired adjacent non-tumor tissues and GC cell lines, and verified the expression trend of YTHDF1 in five GEO GC datasets. YTHDF1 expression and clinical features of GC patients were assessed by the UALCAN. Results: The DMS with high specificity and sensitivity (AUC = 0.986) is proven to distinguish cancer from normal controls better. Moreover, we found that the expression profile variation of YTHDF1 was significantly associated with the high-risk subtype of GC patients. RT-qPCR and Western blot results are consistent with silicon analysis, revealing that YTHDF1's potential oncogene role in GC tumor. Conclusion: In conclusion, we developed the m6A gene-based diagnostic signature for GC and found that YTHDF1 was significantly correlated with the high-risk subtype of GC patients, suggesting that YTHDF1 might be a potential target in GC early diagnosis. Keywords: m6A, RNA methylation, diagnostic signature, YTHDF1, gastric cancer
ISSN:1179-1322
1179-1322
DOI:10.2147/CMAR.S279370