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Background Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein implicated in tumor growth and metastasis in various cancers, including lung adenocarcinoma (LUAD). However, its role in shaping the tumor immune microenvironment and influencing prognosis remains incompletely understood. Here, we aim to investigate TROP2-associated transcriptomic alterations in LUAD and explore their prognostic value and impact on the tumor immune landscape.Methods Transcriptomic and clinical data were retrieved from The Cancer Genome Atlas (TCGA) Lung Adenocarcinoma dataset consisting of 515 samples. Median log 2-transformed TROP2 expression was used to group patients into high vs. low-TROP2 group. Differential expression analysis was used to screen out differentially expressed genes (DEGs) between TROP2 groups. Significant DEGs (|Log2FC| >=1 & adjusted p-value <0.05) was fitted into Cox Proportional Hazard model to screen out prognostic-related TROP2 DEGs. A risk score was calculated using the average summation of the prognostically significant TROP2 DEGs and patients were grouped into high- vs. low-risk groups. Kaplan-Miere plots were used to study survival association between risk groups. The xCELL algorithm was used to estimate the abundance of 62 immune and stromal cells between risk groups. The STRING database was used to predict protein-protein interaction (PPI) network for the risk score genes.Results A total of 696 genes were differentially expressed between TROP2 groups. Ninety DEGs were significantly associated with overall survival and used to calculate the risk score. Patients with low-risk group had a significantly better overall survival (Median OS: 58.4 vs. 35.2, log-rank p-value <0.001). Tumor microenvironment showed that low-risk group had a significantly higher levels of several T-cell subsets (CD4+, CD4+ central memory, CD8+, and Tregs) in addition, innate immune cells such as dendritic cells, NK cells, mast cells and endothelial cells, whereas epithelial cells and keratinocytes were significantly higher in the high-risk group. Gene ontology and PPI network analysis showed significant enrichment in gap junctions, uptake of cobalamin, envelop formation, and keratinocytes.Conclusions TROP2-associated transcriptomic profiling in LUAD reveals distinct immune microenvironment signatures and identifies a gene-based risk score predictive of patient prognosis. These findings support the potential utility of TROP2-related molecular markers for prognostication and therapeutic stratification in LUAD.