Integrated analysis reveals GSTA1 as a prognostic biomarker in stage I lung adenocarcinoma.

BACKGROUND: Postoperative survival in early-stage lung adenocarcinoma (LUAD) remains heterogeneous. Reliable prognostic biomarkers are needed to refine recurrence-risk stratification and guide individualized care. METHODS: We integrated transcriptomic profiles from 274 stage I LUAD tumors and 637 normal lung tissues across three public datasets—Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO)—to identify differentially expressed genes (DEGs) with functional enrichment analyses. Findings were validated in an independent institutional cohort of 226 resected early-stage LUADs using tissue microarrays (TMAs) and immunohistochemistry (IHC). RESULTS: Nine upregulated genes were associated with improved recurrence-free survival (RFS) including glutathione S-transferase alpha 1 (GSTA1). A three-gene model (NQO1, EPHX1, and GSTA1) stratified patients into high- and low-risk groups. TMA analyses confirmed that higher tumor GSTA1 protein expression correlated with longer RFS. GSTA1 expression was also associated with key clinicopathologic features, including smoking history, presence of ground-glass opacity (GGO), pathological stage, and histologic subtype composition. CONCLUSIONS: High GSTA1 expression is associated with a favorable prognosis in stage I LUAD. Clinically, IHC-based GSTA1 scoring can be integrated into the postoperative workflow as a pragmatic risk-stratification aid: low GSTA1, especially when found alongside adverse features (micropapillary/solid patterns, STAS, or absent GGO), may warrant intensified surveillance and a lower threshold for adjuvant-therapy discussion, whereas high GSTA1 supports standard surveillance in otherwise low-risk profiles. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-025-15518-6.