Comprehensive Analysis of YTH Domain Family in Lung Adenocarcinoma: Expression Profile, Association with Prognostic Value, and Immune Infiltration

Abstract

Background. All YTH domain family members are m6A reader proteins accounting for the methylation modulation involved in the process of tumorgenesis and tumor progression. However, the expression profiles and roles of the YTH domain family in lung adenocarcinoma (LUAD) remain to be further illustrated. Methods. GEPIA2 and TNMplot databases were used to generate the expression profiles of the YTH family. Kaplan-Meier plotter database was employed to analysis the prognostic value of the YTH family. Coexpression profiles and genetic alterations analysis of the YTH family were undertaken using the cBioPortal database. YTH family protein-associated protein-protein interaction (PPI) network was identified by using STRING. Functional enrichment analysis was performed with the help of the WebGestalt database. The correlation analysis between the YTH family and immune cell infiltration in LUAD was administrated by using the TIMER2.0 database. Results. mRNA expression of YTHDC1 and YTHDC2 was significantly lower in LUAD, whereas YTHDF1, YTHDF2, and YTHDF3 with apparently higher expression. YTHDF2 expression was observed to be the highest in the nonsmoker subgroup, and its expression gradually decreased with the increased severity of smoking habit. LUAD patients with low expression of YTHDC2, YTHDF1, and YTHDF2 were correlated with a better overall survival (OS) time. The YTHDF1 genetic alteration rate was 26%, which was the highest in the YTH family. The major cancer-associated functions of YTH family pointed in the direction of immunomodulation, especially antigen processing and presentation. Most of the YTH family members were significantly correlated with the infiltration of CD4+ T cells, CD8+ T cells, macrophages, and neutrophils, indicating the deep involvement of the YTH domain family in the immune cell infiltration in LUAD. Conclusion. The molecular and expression profiles of the YTH family were dysregulated in LUAD. YTH family members (especially YTHDC2) were promising biomarkers and potential therapeutic targets that may bring benefit for the patients with LUAD.

Host Factor Interaction Networks Identified by Integrative Bioinformatics Analysis Reveals Therapeutic Implications in COPD Patients With COVID-19

“…We conducted gene ontology (GO) analysis and pathway enrichment analysis to characterize the biological mechanisms and signaling pathways of common host factor networks. GO biological processes and GO molecular functions are drawn by the WEB-based genome analysis toolkit webgestalt ( Hu et al, 2021 ) ( http://www.webgestalt.org/ ), and the KEGG pathway analysis results are generated by R and clusterprofiler ( Yu et al, 2012 ) package. A cutoff of Benjamini-Hochberg adjusted p -values < 0.05 was adopted in this apart.…”

YTHDC1 m6A-dependent and m6A-independent functions converge to preserve DNA damage response.

“…Additionally, the recognition that there are both m6A-dependent and m6A-independent mechanisms involved in DDR and further understanding of these pathways may be helpful for the development of potential novel therapies. Aberrant m6A modification is prevalent in various types of cancer and is associated with patient prognosis (Hu et al, 2021; W. Li et al, 2022; Meng et al, 2020).…”

Integrative Analysis of the Predictive Value of Perilipin Family on Clinical Significance, Prognosis and Immunotherapy of Glioma

“…Previous studies have demonstrated that in some cancer types, the infiltration of lymphocytes, especially CD4 + T cells and CD8 + T cells, was associated with the activation of immune responses and resulted in favorable prognosis. Meanwhile, the tumor lesion infiltration of large numbers of tumor-associated neutrophils may induce inflammation and stimulate tumor progression and metastasis, thus inhibiting anti-tumor T-cell responses [ 55 , 56 ]. Macrophages are multifunctional immune cells that have the function of phagocytosis and digestion of foreign substances.…”