Zhou Li, Yanqi Feng, Piao Li, Shennan Wang, Xinyue Liu, Shu Xia Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Shu Xia, Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, People’s Republic of China, Tel +86 15827110062, Fax +86 27-83662834, Email xiashutj@hotmail.comPurpose: Tumor mutation burden (TMB) and tumor-infiltrating lymphocytes (TILs) have been well recognized as molecular determinants of immunotherapy responsiveness. In this study, we aimed to construct a TMB prognostic model and explore biomarkers that have predictive potential for prognosis and therapeutic effect in lung adenocarcinoma (LUAD).Patients and Methods: The TCGA, GEO and Immport databases were used to analyze the mutation profiles and immune infiltration of LUAD. TMB scores were calculated and differential analysis was conducted to identify TMB-related genes. Then, Cox regression model and survival analysis were applied to identify the prognostic genes and construct a TMB prognostic model. The expression and prognostic value of CD1B were further verified by immunohistochemistry (IHC) in 92 patient tissue samples. GSEA was performed to analyze the signaling pathways associated with CD1B expression.Results: High-TMB samples exhibited higher infiltration of CD8+ T cells, CD4+ memory T cells, and M1 macrophages. A total of 397 TMB-related differentially expressed genes were identified, of which 47 were immune-related genes. Cox regression analyses determined 3 hub TMB-related immune genes (CD1B, SCGB3A1, and VEGFD) with prognostic effects, and a TMB prognostic model was constructed. The model demonstrated robust predictive ability in both the training (TCGA) and testing (GEO) datasets. Notably, CD1B was identified as an independent prognostic factor. IHC of clinical samples showed that low expression of CD1B was related to poor overall survival and advanced pathological stages. In addition, there was a strong positive correlation between CD1B and most immune checkpoint molecules, including PD-L1. CD1B expression was associated with immune cell infiltration and immune activation in LUAD.Conclusion: Our study constructed a TMB prognostic model that effectively predicted the prognosis of LUAD patients. CD1B expression is correlated with better prognosis and promotes antitumor immunity in LUAD, which may serve as a potential prognostic biomarker and immune-related therapeutic target for LUAD.Keywords: lung adenocarcinoma, tumor mutation burden, CD1B, prognosis, immune infiltrates
