Spatial and Single-Cell Analyses Reveal Correlation between Histone H2A Dioxygenase Gene Expression and Tumor-Associated Macrophages in Gastric Cancer

AbstractBackgroundALKBH1 is an important enzyme involved in various cellular processes that regulates RNA demethylation in humans. While its contribution to tumor progression is known, its role in gastric cancer remains unclear. Further research is needed to explore the potential of ALKBH1 in clinicopathology, tumor immune microenvironment, and precision oncology for STAD.MethodsThis study used a multi-omics approach to identify ALKBH1 as an independent diagnostic biomarker for STAD with a correlation to advanced clinical status and poor overall survival rate. We analyzed publicly available datasets from GEO and TCGA, identifying differentially expressed genes in STAD and examined their relationship with immune gene expression, overall survival, tumor stage, gene mutation status, and infiltrating immune cells. We also explored ALKBH1 gene expression in different regions of the STAD using spatial transcriptomics. In addition, we utilized spatial transcriptomic and single-cell RNA-sequencing methods to investigate the correlation between PGAM1 and immune cells. We further confirmed our results by analyzing 60 STAD patient samples and examining the relationship between ALKBH1 expression, clinicopathological features, and prognosis using immunohistochemistry and bioinformatics.ResultsOur study revealed the expression of key gene regulators in gastric cancer that were associated with genetic variations, deletions, and the tumor microenvironment. Mutations in these regulators were positively linked to distinct immune cells in six immune datasets and played a vital role in immune cell infiltration in STAD. We found that high ALKBH1 expression was associated with macrophage infiltration in STAD. Moreover, pharmacogenomic analysis of renal cancer cell lines indicated that ALKBH1 inactivation was correlated with increased sensitivity to specific small-molecule drugs.ConclusionTo sum up, the study indicates that alterations in ALKBH1 may play a role in STAD advancement and reveal new diagnostic and prognostic implications of ALKBH1 in STAD. It emphasizes the importance of ALKBH1 in the tumor immune microenvironment, implying its potential utility as a precision medicine tool and for drug screening in STAD.