FASTKD1 is a diagnostic and prognostic biomarker for STAD associated with m6A modification and immune infiltration

Abstract

Background Fas Activated Serine/Threonine Kinase Domains 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 objective of this study is to investigate the relationship between FASTKD1 expression and key factors including clinical pathologies, immune infiltration, and m6A modification in stomach adenocarcinoma (STAD). Methods We analyzed the expression of FASTKD1 in stomach adenocarcinoma and normal adjacent tissue to assess its significance in clinical pathologies 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 (IHC) 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. An in-depth analysis was conducted using reputable databases such as TIMER, GEPIA, and TCGA to explore the potential correlation between FASTKD1 expression and immune infiltration in STAD. Additionally, we analyzed TCGA and GEO data to explore the correlation between FASTKD1 expression levels and m6A modifications in STAD. Results FASTKD1 demonstrates significant upregulation across different tumor types, including STAD. Notably, it can distinguish between tumor and normal tissue samples with accuracy. The expression level of FASTKD1 correlates significantly with clinical stage and survival prognosis. Through GO/KEGG enrichment analysis, associations of FASTKD1 have been identified with nuclear chromosome segregation, chromosomal regions, catalytic activity (acting on RNA), ATPase activity, as well as cell cycle and spliceosome pathways. The GSEA analysis revealed that in STAD, FASTKD1 is linked to gene enrichment pathways, mainly including the retinoblastoma gene, activation of ATR in response to replicative stress, resolution of D-loop structures, PLK1 pathway, homologous DNA pairing and strand exchange, and nuclear pore complex disassembly. Within the TIMER, GEPIA, and TCGA databases, a notable inverse correlation has been observed between FASTKD1 expression and the abundance of immune cell subsets, such as CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Of particular interest, significant correlations are established between FASTKD1, and m6A modification genes YTHDF1 and LRPPRC in both TCGA and GEO datasets. Conclusion FASTKD1 plays a significant role in m6A modification and immune infiltration processes, making it a potential valuable diagnostic and prognostic biomarker in stomach adenocarcinoma.