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Comprehensive Analysis of Expression and Prognostic Value of GATAs in Lung Cancer.

ABSTRACT: GATAs are a family of transcription factors that play sophisticated and extensive roles in cell fate transitions and tissue morphogenesis during embryonic development. Emerging evidence indicate that GATAs are involved in tumorigenesis of lung cancer (LC). However, the distinct roles, diverse expression patterns and prognostic values of six GATA family members in LC have yet to be elucidated. In the present study, the diverse expression patterns, prognostic values, genetic mutations, protein-protein interaction(PPI) networks of GATAs, Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway in LC patients were analyzed using a serious of databases, including ONCOMINE database, Cancer Cell Line Encyclopedia database, the Human Protein Atlas, the Gene Expression Profiling Interactive Analysis database, the Kaplan-Meier plotter, cBioPortal, String database and database Database for Annotation, Visualization, and Integrated Discovery. The mRNA expression levels of GATA1/2/4/5/6 were downregulated, while GATA3 showed abnormal expressions of up-regulation and down-regulation in patients with LC. Aberrant GATAs mRNA expression was connected with prognosis. Furthermore, genetic alterations mainly appeared in GATA4. Gene Ontology enrichment and network analysis demonstrated that GATAs and their 50 interactors were primarily associated with positive regulation of transcription from RNA polymerase II promoter, transcription factor complex, transcription factor binding Jak-STAT signaling pathway. This comprehensive bioinformatic analysis demonstrated that GATA1/2/3/4/6 may be new prognosis factors, and GATA2/5/6 may be potential targets for personalized therapy for patients with LC, but further studies are requisite to analyze the mechanism of their carcinogenicity and investigate novel drug treatment. Finally, these findings would conduce to a better understanding of the unique roles of GATAs in LC.

SUBMITTER: Gong C

PROVIDER: S-EPMC8176258 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAll 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.MethodsGEPIA2 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.ResultsmRNA 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.ConclusionThe 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.

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Comprehensive Analysis of Expression and Prognostic Value of GATAs in Lung Cancer.

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