[ITK is a potential prognostic biomarker in lung adenocarcinoma related to the tumor immune microenvironment]

Objective To investigate the expression characteristics of the interleukin 2-inducible T-cell kinase (ITK) gene in lung adenocarcinoma (LUAD), its clinical prognostic value, and its potential role in the tumor microenvironment. Methods ITK expression data were obtained from the TCGA and GEO datasets (GSE75037, GSE32863) to analyze its differential expressions between LUAD and adjacent normal tissues. The TCGA-LUAD cohort was used for survival analysis, clinicopathological correlation analysis, and to construct an integrated nomogram prognostic model combining ITK expression with clinical features via Cox regression. The TIMER and CIBERSORT algorithms were employed to assess the correlation between ITK expression and immune cell infiltration. GSEA enrichment analysis was used to compare pathway differences between the high and low ITK expression groups. Results ITK expression was significantly lowered in multiple cancers including LUAD, and its low expression was associated with poor prognosis of patients. Clinical analysis revealed that ITK expression was significantly correlated with tumor Stage grade and T stage. The constructed nomogram model demonstrated good predictive performance (C-index=0.67). High ITK expression showed a significant positive correlation with increased infiltration of anti-tumor immune cells such as CD8⁺ T cells and M1 macrophages. Pathway enrichment analysis indicated that the high ITK expression group was primarily enriched in immune-related pathways like inflammatory response and interferon-gamma signaling, whereas the low expression group was enriched in metabolic reprogramming processes such as fatty acid metabolism and glycolysis. Conclusion ITK is a potential independent prognostic biomarker in LUAD. Its loss of expression may be associated with suppressed tumor immune microenvironment and activated metabolic reprogramming, thereby promoting tumor progression. ITK may serve as a novel target for prognostic assessment and immunotherapy research in LUAD.