Background: Gastric cancer (GC) is an important cause of death. Molecular targeted therapy and immunotherapy are progressing rapidly. It is very important to explore the pathogenesis pathways of GC and provide strong support for its treatment. However, the mechanism of occurrence and development of GC is still unclear.
Methods: Online databases and immunohistochemistry (IHC) of clinical samples were used to analyze the differential expression of YTHDF1 in the GC and nearby tissues, and its effect on survival prognosis. In vitro experimental study of GC, other mechanisms and functional analyses were specifically designed and performed too.
Results: Online data and clinical samples analysis showed that the expression of YTHDF1 in GC was markedly elevated compared to surrounding tissues. Higher YTHDF1 levels were correlated with worse survival outcomes. Analysis of correlation with clinical parameters showed that the expression level of YTHDF1 exhibited a favorable correlation with lymphatic metastases, as well as with PD-1 and PD-L1 levels. In vitro studies of YTHDF1 overexpression have demonstrated its ability to enhance GC cell growth and migration while inhibiting apoptosis. Based on our results, RELA is a downstream target of YTHDF1, and YTHDF1 triggers the NF-κB signaling pathway by regulating RELA translation.
Conclusion: In comparison to adjacent tissues, GC exhibits significantly elevated YTHDF1 expression. Increased YTHDF1 expression in the GC is correlated with decreased patient survival. Lymph node metastasis and the expression of PD-1 and PD-L1 are positively correlated with YTHDF1 levels. YTHDF1 inhibits apoptosis while promoting the migration and proliferation of GC. Additionally, it stimulates the NF-κB pathway and controls the translation of RELA.
Keywords: NF‐kappa B signaling pathway; RELA; YTHDF1; gastric cancer.
© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.