Identification of JAML as an Immune-Associated Prognostic Marker in Non-Small Cell Lung Cancer.
INTRODUCTION: Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related mortality worldwide, and the identification of novel prognostic biomarkers associated with tumor immunity is urgently needed. Junctional adhesion molecule-like (JAML), a member of the junctional adhesion molecule family, participates in leukocyte adhesion, migration, and T-cell activation. Although JAML has been implicated in immune regulation and tumor progression in other cancers, its expression pattern, prognostic significance, and association with the immune microenvironment in NSCLC remain unclear. This study aimed to investigate the clinical and immunological significance of JAML in NSCLC. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to evaluate JAML expression patterns in NSCLC subtypes. The prognostic value of JAML was assessed using Kaplan-Meier survival analysis and Cox regression models. The association between JAML expression and immune cell infiltration was investigated using TIMER2.0, CIBERSORT, and TISIDB analyses. Functional enrichment analyses were performed to explore potential biological pathways associated with JAML expression. In addition, JAML expression was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in paired NSCLC and adjacent normal tissues. RESULTS: JAML expression was significantly decreased in NSCLC tissues compared with normal tissues (P < 0.005), with the lowest expression observed in lung squamous cell carcinoma (LUSC) and reduced expression in lung adenocarcinoma (LUAD). Survival analysis demonstrated that patients with high JAML expression had significantly improved overall survival compared with those with low expression (univariate HR = 0.68, 95% CI: 0.54-0.86, P = 0.001; multivariate HR = 0.76, 95% CI: 0.57-1.00, P = 0.049). Immune infiltration analysis revealed that JAML expression was significantly associated with multiple immune cell populations, including CD8+ T cells (r = 0.42, P < 0.001), suggesting a close relationship between JAML expression and the tumor immune microenvironment. qRT-PCR validation confirmed that JAML expression was approximately 2.3-fold higher in adjacent normal tissues than in NSCLC tissues (P < 0.05). CONCLUSION: JAML is downregulated in NSCLC and its high expression is associated with favorable overall survival and distinct immune infiltration patterns. These findings indicate that JAML may serve as a potential prognostic biomarker and provide insights into the relationship between JAML expression and the tumor immune microenvironment in NSCLC.