FASTKD1 as a diagnostic and prognostic biomarker for STAD: Insights into m6A modification and immune infiltration

Exp Ther Med. 2024 May 31;28(2):305. doi: 10.3892/etm.2024.12594. eCollection 2024 Aug.

Abstract

Fas-activated serine/threonine kinase domain 1 (FASTKD1), a known modulator of mitochondrial-mediated cell death and survival processes, has garnered attention for its potential role in various biological contexts. However, its involvement in gastric cancer remains unclear. Thus, the present study aimed to investigate the relationship between FASTKD1 expression and key factors, including clinicopathological characteristics, immune infiltration and m6A modification in stomach adenocarcinoma (STAD). The expression of FASTKD1 was analyzed in STAD and normal adjacent tissues to assess its association with clinicopathological characteristics and survival prognosis. Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used in this study. Additionally, the findings were validated through immunohistochemical staining. Co-expression analysis of FASTKD1 was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment analysis, Gene Set Enrichment Analysis (GSEA) and LinkedOmics database analysis. An in-depth analysis was conducted using databases, such as Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), GEO and TCGA to explore the potential correlation between FASTKD1 expression and immune infiltration and m6A modification in STAD. The results revealed that FASTKD1 was significantly upregulated across different tumor types, including STAD. Notably, FASTKD1 was able to distinguish between tumor and normal tissue samples with accuracy. Furthermore, the expression levels of FASTKD1 were significantly associated with clinical stage and survival. Through GO/KEGG enrichment analysis and GSEA, it was revealed that the genes co-expressed with FASTKD1 were active in a variety of biological processes. Within the TIMER, GEPIA and TCGA databases, a notable inverse correlation was observed between FASTKD1 expression and the abundance of immune cell subsets. Notably, significant correlations were established between FASTKD1 and m6A modification genes, YTHDF1 and LRPPRC, in both TCGA and GEO datasets. In conclusion, FASTKD1 may serve a significant role in m6A modification and immune infiltration processes, making it a potentially valuable diagnostic and prognostic biomarker in STAD.

Keywords: Fas-activated serine/threonine kinase domain 1; diagnostic and prognostic biomarker; immune infiltration; m6A modification; stomach adenocarcinoma.

Grants and funding

Funding: This work was supported by the Hubei Province's Outstanding Medical Academic Leader program, the Foundation for Innovative Research Team of Hubei Provincial Department of Education (grant no. T2020025), the Free-exploring Foundation of Hubei University of Medicine (grant no. FDFR201903), the Innovative Research Program for Graduates of Hubei University of Medicine (grant nos. YC2023007 and YC2023035), and the Key Discipline Project of Hubei University of Medicine.