Expression, Prognostic Significance, and Immune-Related Roles of ABCA Family Genes in Gastric Cancer: A Comprehensive Analysis.

Background: Previous studies have demonstrated that ABCA family proteins play a critical role in cholesterol transport. Cholesterol, as a major component of the cell membrane, can influence numerous physiological and pathological processes, including cell migration, cancer progression, and metastasis. Therefore, ABCA family proteins may impact cancer progression; however, their specific roles in gastric cancer remain poorly understood. Methods：In this study, we systematically assessed the expression, prognostic significance, and immune-related implications of ABCA family genes in gastric cancer (GC). Utilizing data from The Cancer Genome Atlas (TCGA) database, we compared ABCA expression profiles between GC and normal gastric mucosa. We conducted Kaplan-Meier analysis, Cox regression, and logistic regression to investigate associations with clinical characteristics, constructed ROC curves and nomograms for diagnostic evaluation, and single sample gene set enrichment analysis (ssGSEA) algorithm assessed ABCA relationships with immune cell infiltration, immune-related genes, immune checkpoint genes, the tumor immune dysfunction and exclusion (TIDE) predicts response to immuno-check inhibitor therapy, "oncoPredict" function for chemotherapy drug resistance analysis. We also employed Gene Set Enrichment Analysis (GSEA) to evaluate relevant signaling pathways. To validate our findings, we performed PCR to confirm ABCA expression in gastric cancer and normal gastric mucosal cells.

Results: Our results demonstrate significant differential expression of most ABCA family members in GC tissues compared to normal tissues, with associations to clinicopathological parameters. Cellular experiments revealed distinct expression patterns of ABCA genes in GC cell lines, with some aligning with TCGA data and others showing variability. Differentially expressed transcripts correlated with overall survival, making ABCAs independent risk factors for GC patient survival. A validated nomogram predicted overall survival. ABCAs exhibited correlations with immune cell infiltration, co-expression with immune-associated and checkpoint genes, and implications for resistance to common therapies and immunotherapy. Enrichment analysis highlighted pathways involving the extracellular matrix, cell motility, cell death, and tumor development.

Conclusion: In conclusion, ABCA family genes hold promise as prognostic biomarkers and potential immunotherapeutic targets due to their relevance in the tumor microenvironment, particularly in relation to immune cell infiltration.