Pan-cancer evaluation of ABAT as an emerging biomarker and its implication in lung adenocarcinoma

4-aminobutyric acid aminotransferase (ABAT) is a pivotal enzyme for mitochondrial metabolism and central nervous system homeostasis, with known links to neurotransmitter regulation and mental illnesses. However, its role in cancer remains understudied. This study aims to comprehensively evaluate ABAT's pan-cancer landscape-including gene expression, diagnostic-prognostic value, epigenetic modifications, immune infiltration, and drug sensitivity-and validate its functional role in lung adenocarcinoma (LUAD).

Using multi-omics data from TCGA (The Cancer Genome Atlas), HPA (Human Protein Atlas), UALCAN (University of Alabama at Birmingham Library Cancer Analysis Portal), TIMER2.0 (Tumor IMmune Estimation Resource 2.0), and other databases, we conducted bioinformatics analyses to characterize ABAT across 33 cancer types. In vitro validation involved quantitative real-time polymerase chain reaction (qRT-PCR) and transwell assays to assess ABAT expression, migration, and invasion in LUAD tissues and cell lines.

ABAT was significantly underexpressed in 11 cancers [e.g., kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), LUAD] and overexpressed in [breast invasive carcinoma (BRCA)/pheochromocytoma/paraganglioma (PCPG)], with expression correlating with tumor staging (e.g., stage III LUAD). It exhibited high diagnostic accuracy [area under curve (AUC) >0.8] in 5 cancers [cholangiocarcinoma (CHOL), kidney chromophobe carcinoma (KICH)] and predicted poor prognosis in KIRC, LUAD, etc. Promoter hypermethylation negatively correlated with ABAT expression in most cancers. ABAT associated with CD8⁺/CD4⁺ T cell infiltration, 17 immune checkpoints (e.g., ADO, CD160), and differential drug sensitivity (e.g., afatinib sensitivity in ABAT-high cells). In LUAD, ABAT overexpression inhibited cell migration and invasion.

ABAT shows expression heterogeneity in pan-cancer, linking to diagnosis, prognosis, immune microenvironment, and drug response. Its tumor-suppressive role in LUAD highlights ABAT as a potential biomarker and therapeutic target for precision oncology, warranting further clinical validation.