ArticleTranslational cancer research2026
Identification and validation of ZAP70 as a potential biomarker associated with T cell infiltration in lung adenocarcinoma.
Article in Translational cancer research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Zeta-chain-associated protein kinase 70 kDa (ZAP70) is a tyrosine kinase essential for T cell activation and differentiation and it is predominantly expressed in T cells. However, its clinical relevance and relationship with the immune microenvironment in lung adenocarcinoma (LUAD) remain unclear. Therefore, this study aimed to investigate the expression profile of ZAP70 in LUAD, evaluate its prognostic significance, and explore its correlation with the tumor immune microenvironment. Methods: Transcriptomic and clinical data for LUAD were obtained from The Cancer Genome Atlas (TCGA) and supplemented with Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC) data, and Human Protein Atlas (HPA) resources. The messenger RNA (mRNA) and protein levels of ZAP70 were further validated in seven paired LUAD and adjacent normal tissues. Results: Pan-cancer analysis revealed heterogeneous ZAP70 expression, with significantly reduced mRNA and protein levels in lung cancer, including LUAD. In LUAD, low ZAP70 expression was associated with advanced T stage, stage IV disease, M1 metastasis, and inferior overall survival, first progression, and post-progression survival. The Tumor Immune Estimation Resource (TIMER) analysis showed that higher ZAP70 expression correlated with increased infiltration of multiple immune cell types. Single-cell transcriptomic profiling demonstrated that ZAP70 was predominantly expressed in T cells, with LUAD tissues displaying altered T cell subset composition and an increased proportion of ZAP70low T cells compared with normal lung. Functional enrichment indicated that ZAP70-related genes were involved in cell cycle and immune-related pathways. Consistently, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays confirmed reduced ZAP70 expression in LUAD tissues, particularly in patients with more advanced disease. Conclusions: These findings suggest that ZAP70 may serve as a potential biomarker and therapeutic target in LUAD, warranting further mechanistic and prospective clinical studies.
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