<p>The N6-Methyladenosine (m6A) Methylation Gene <em>YTHDF1 </em>Reveals a Potential Diagnostic Role for Gastric Cancer</p>

Abstract

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 YTHDF1'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.

The roles and mechanisms of the m6A reader protein YTHDF1 in tumor biology and human diseases

“… 58 The expression profile variation of YTHDF1 is significantly associated with the high-risk subtype of GC patients, revealing the potential oncogene roles of YTHDF1 in GC tumors. 59 There is an approximately 7% mutation rate in YTHDF1 in GC patients, and high expression of YTHDF1 is correlated with more aggressive tumor progression and poor overall survival. 38 …”

NF-κB-Related Metabolic Gene Signature Predicts the Prognosis and Immunotherapy Response in Gastric Cancer

“…Glioma was classified into low and high hypoxia risk groups according to hypoxia signature, which was also associated with patients' OS [ 49 ]. Moreover, previous research used various gene sets, including glycolysis-related gene set, cell cycle-related gene set, angiogenesis-related gene set, and N6-methyladenosine methylation gene set, to achieve classification of GC [ 50 – 53 ]. All of these classification could effectively forecast patients' prognosis.…”

N6‐methyladenosine Steers RNA Metabolism and Regulation in Cancer

“…Pei et al [162] also detected elevated m 6 A level in the peripheral blood leukocyte from non-small cell lung cancer patients by flow cytometry, indicating the potential use of m 6 A as a non-invasive biomarker. Furthermore, m 6 A regulators, including METTL3 [77,[163][164][165][166][167][168][169], WTAP [170][171][172][173], FTO [174][175][176][177], IGF2BPs [178][179][180][181][182][183][184], and YTHDFs [73,[185][186][187][188][189][190][191][192], have been proven to associate with favorable or unfavorable prognosis in different types of cancers (detailed in Section 3). It should be noted that prognosis is not simply associated with the expression of a certain gene but a comprehensive signature of multiple m 6 A regulators in cancers, including lung cancer [163,164], pancreatic cancer [166,193], and HCC [194].…”