A robust CD8+ T cell-related classifier for predicting the prognosis and efficacy of immunotherapy in stage III lung adenocarcinoma

Abstract

Patients with stage III lung adenocarcinoma (LUAD) have significant survival heterogeneity, meanwhile, CD8⁺ T cell has a remarkable function in immunotherapy. Therefore, developing novel biomarkers based on CD8⁺ T cell can help evaluate the prognosis and guide the strategy of immunotherapy for patients with stage III LUAD. Thus, we abstracted twelve datasets from multiple online databases and grouped the stage III LUAD patients into training and validation sets. We then used WGCNA and CIBERSORT, while univariate Cox analysis, LASSO analysis, and multivariate Cox analysis were performed. Subsequently, a novel CD8⁺ T cell-related classifier including HDFRP3, ARIH1, SMAD2, and UPB1 was developed, which could divide stage III LUAD patients into high- and low-risk groups with distinct survival probability in multiple cohorts (all P < 0.05). Moreover, a robust nomogram including the traditional clinical parameters and risk signature was constructed, and t-ROC, C-index, and calibration curves confirmed its powerful predictive capacity. Besides, we detected the difference in immune cell subpopulations and evaluated the potential benefits of immunotherapy between the two risk subsets. Finally, we verified the correlation between the gene expression and CD8⁺ T cells included in the model by immunohistochemistry and validated the validity of the model in a real-world cohort. Overall, we constructed a robust CD8⁺ T cell-related risk model originally which could predict the survival rates in stage III LUAD. What's more, this model suggested that patients in the high-risk group could benefit from immunotherapy, which has significant implications for accurately predicting the effect of immunotherapy and evaluating the prognosis for patients with stage III LUAD.

Keywords: CD8+ T cell; classifier; immunotherapy; lung adenocarcinoma; prognosis.