Frontiers in Medical Science Research, 2026, 8(2); doi: 10.25236/FMSR.2026.080207.
Nan Wu1, Linyong Du2
1College of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, China
2Key Laboratory of Laboratory Medicine, Ministry of Education, College of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide, highlighting an urgent need for robust prognostic biomarkers to guide clinical decision-making. In this study, we integrated single-cell RNA sequencing (GSE131907) with bulk transcriptomic data from The Cancer Genome Atlas (TCGA)-LUAD cohort to construct an immune-related prognostic signature. Through comprehensive analysis of 86,145 single cells, we established a LUAD atlas and identified immune-related genes by intersecting single-cell markers with the ImmPort database. Univariate Cox regression and LASSO penalized Cox analysis revealed a four-gene signature comprising PITX3, DKK1, TLE1, and LDHA, which stratified patients into high- and low-risk groups with significantly different overall survival outcomes (Log-rank P < 0.001). The signature exhibited robust predictive accuracy with area under the curve values of 0.713, 0.695, and 0.640 for 1-, 3-, and 5-year survival, respectively. Immune infiltration analysis using the xCell algorithm demonstrated that the low-risk group was enriched with anti-tumor immune cells, including CD8+ T cells and dendritic cells, while the high-risk group showed higher infiltration of immunosuppressive components. Furthermore, the risk score was positively correlated with immune checkpoint molecules such as PDCD1 and LAG3, suggesting an association with T-cell exhaustion and immune evasion. In summary, this four-gene immune-related signature serves as a promising prognostic biomarker for LUAD, offering valuable insights into the tumor immune microenvironment and potential implications for personalized immunotherapy strategies.
Lung Adenocarcinoma; Prognostic Signature; Single-Cell Analysis; Immune Checkpoint
Nan Wu, Linyong Du. A Novel Immune-Related Four-Gene Signature for Prognosis and Immune Infiltration in Lung Adenocarcinoma. Frontiers in Medical Science Research (2026), Vol. 8, Issue 2: 49-58. https://doi.org/10.25236/FMSR.2026.080207.
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