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Orgilmaa Regzedmaa,1,* Ying Li,2,* Yongwen Li,2,* Hongbing Zhang,1 Jin Wang,2 Hao Gong,1 Yin Yuan,1 Weiting Li,1 Hongyu Liu,2 Jun Chen1,2 1Department of Lung Cancer Surgery, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Medical University General Hospital, Tianjin 300052, People’s Republic of China; 2Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Chen; Hongyu LiuTianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Heping District, Tianjin 300052, People’s Republic of ChinaEmail huntercj2004@yahoo.com; liuhongyu123@hotmail.comIntroduction: Immune-based and antibody-drug conjugate therapies have shown promise in the treatment of patients with small cell lung cancer (SCLC). However, better predictive biomarkers are needed for selection of the appropriate SCLC patients for these advanced therapies and also for evaluation of the efficacy of these treatments.Objective: The aim of this study was to examine the expression of delta-like protein 3 (DLL3), cytotoxic T lymphocyte-associated protein 4 (CTLA-4), and mesothelin (MSTN) in patients with SCLC and compare them with those patients’ clinical characteristics.Methods: Immunohistochemical analyses of DLL3, CTLA-4 and MSTN expression were performed in 38 samples from patients with SCLC.Results: We found that positive expression in patients of the biomarkers was as follows: for DLL3, 100% (38/38), for CTLA-4, 89.5% (36/38) and for MSTN 81.5% (31/38). The median survival time was 17.9 months in the DLL3 high expression group and 23 months in the DLL3 low expression group. Patients with a high expression of DLL3 showed a poorer prognosis than those with a low expression of DLL3 (HR=3.4; 95% CI, 1.34–8.6; p=0.01).Conclusion: The expression of DLL3, CTLA-4 and MSTN was not correlated with patients’ age, sex, smoking status, stage, and tumor metastasis. The fact that there was a higher expression of DLL3, CTLA-4, and MSTN in SCLC suggested that these molecules could be used as predictive biomarkers for SCLC.Keywords: small cell lung cancer, DLL3, CTLA-4, MSTN, prognosis