Comprehensive Analysis of YTHDF1 Immune Infiltrates and ceRNA in Human Esophageal Carcinoma

Xu-Sheng Liu; Xue-Yan Kui; Yan Gao; Xue-Qin Chen; Jing Zeng; Xiao-Yu Liu; Yu Zhang; Yao-Hua Zhang; Zhi-Jun Pei

doi:10.3389/fgene.2022.835265

Comprehensive Analysis of YTHDF1 Immune Infiltrates and ceRNA in Human Esophageal Carcinoma

Front Genet. 2022 Mar 23:13:835265. doi: 10.3389/fgene.2022.835265. eCollection 2022.

Authors

Xu-Sheng Liu¹, Xue-Yan Kui², Yan Gao¹, Xue-Qin Chen³, Jing Zeng⁴, Xiao-Yu Liu¹, Yu Zhang¹, Yao-Hua Zhang¹, Zhi-Jun Pei^{1

5}

Affiliations

¹ Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
² Postgraduate Training Basement of Jinzhou Medical University, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
³ Hubei University of Medicine, Shiyan, China.
⁴ Department of Infection Control, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
⁵ Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China.

Abstract

Background: YTHDF1 is highly expressed in multiple tumors and affects tumor progression. However, there are only a few comprehensive studies on the analysis of YTHDF1 in esophageal cancer. Methods: We analyzed YTHDF1 expression in pan-cancer by comparing both the GEPIA and TCGA cohorts, and further verified the differences in YTHDF1 expression between the ESCA and normal groups by the GEO ESCA cohort and in vitro experiments. The correlation of YTHDF1 expression and the clinical characteristics of ESCA patients was analyzed using the TCGA ESCA clinical data. The GO and KEGG enrichment analyses of the YTHDF1 coexpressed genes were completed by bioinformatics analysis, and the GGI and PPI were constructed for the YTHDF1, respectively. The relationship between YTHDF1 expression and the infiltration of ESCA immune cells was analyzed by using the TIMER database and the TCGA ESCA cohort. The relationships between YTHDF1 expression levels and glycolysis and ferroptosis-related genes were analyzed using the TCGA and GEPIA ESCA cohorts. Finally, the ceRNA network that may be involved in YTHDF1 in ESCA was predicted and constructed through a variety of databases. Results: YTHDF1 was overexpressed in various cancers, and in vitro experiments confirmed that YTHDF1 expression was higher in ESCA samples than in normal samples. The expression of YTHDF1 has some accuracy in predicting the tumor outcome. Expression of YTHDF1 was significantly associated with multiple clinical features in ESCA patients. GO and KEGG enrichment analyses indicated that YTHDF1 coexpressed genes involved multiple biological functions. There is a potential association between YTHDF1 expression and multiple immune cell infiltration, glycolysis, and ferroptosis-related genes in ESCA. YTHDF1 may be involved in multiple ceRNA regulatory networks in ESCA, including PAXIP1-AS1/hsa-miR-376c-3p/YTHDF1 axis, THUMPD3-AS1/hsa-miR-655-3p/YTHDF1 axis, and SNHG20/hsa-miR-655-3p/YTHDF1 axis, respectively. Conclusion: YTHDF1 can serve as a biomarker of ESCA, related to the immune cell infiltration of ESCA, regulation of glycolysis and ferroptosis, and the ceRNA regulatory network.

Keywords: YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1); ceRNA; esophageal carcinoma; ferroptosis; immune infiltrates.