N6-methyladenosine binding protein YTHDF2 inhibits gastric cancer cell growth and predicts better prognosis in patients with gastric cancer.

BACKGROUND: The potential role of N6-methyladenosine (m6A) in cancer progression has received significant attention in the past few years. The purpose of this study aimed to evaluate the impact of YTH N6-methyladenosine RNA-binding protein 2 (YTHDF2) on patient prognosis and its potential role in gastric cancer. METHODS: A total of 305 patients with clinically informative gastric cancer were identified from The Cancer Genome Atlas (TCGA) dataset, and GSE29272 and GSE84437 were used as external validation. Different m6A modulators were analyzed using the Limma package; the Cox regression models were used to determine risk factors for overall survival (OS). A 1:1 propensity score matching (PSM) analysis was used to adjust for differences in baseline clinicopathological characteristics between the YTHDF2 low and high expression groups. The Cox regression analysis was then used to identify risk factors for OS. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to explore the potential role and function of YTHDF2 in gastric cancer. And the effects of YTHDF2 on the growth of gastric cancer cells were detected in vivo and in vitro. RESULTS: Nineteen m6A methylation regulators were expressed in gastric cancer tissues; YTHDF2 was associated with the prognosis of gastric cancer patients. The expression level of YTHDF2, patient age, and tumor stage were independent risk factors for OS. After PSM, YTHDF2 expression led to a relatively better prognosis and staging. Patients in stage IV had a significantly worse prognosis. The expression of YTHDF2 was associated with cancer-related functions and pathways in gastric cancer. We found that YTHDF2 has lower expression in gastric cancer cells and inhibits the growth of GC cells. CONCLUSIONS: The high expression of YTHDF2 can predict a better prognosis of gastric cancer patients. YTHDF2 exerts a critical role in gastric cancer progression by inhibiting the growth of GC cells.