CD39: the potential target in small cell lung cancer

Shanhao Chen; Shengyu Wu; Liping Zhang; Wei Zhang; Yu Liu; Bin Chen; Sha Zhao; Wei Li; Chenglong Sun; Lei Wang; Keyi Jia; Hao Wang; Peixin Chen; Chunyan Wu; Junjie Zhu; Yayi He; Caicun Zhou

doi:10.21037/tlcr-20-798

CD39: the potential target in small cell lung cancer

Transl Lung Cancer Res. 2020 Aug;9(4):1483-1495. doi: 10.21037/tlcr-20-798.

Authors

Shanhao Chen¹, Shengyu Wu^{2

3}, Liping Zhang⁴, Wei Zhang⁴, Yu Liu^{2

3}, Bin Chen², Sha Zhao², Wei Li², Chenglong Sun^{2

5}, Lei Wang², Keyi Jia^{2

3}, Hao Wang^{2

3}, Peixin Chen^{2

3}, Chunyan Wu⁴, Junjie Zhu⁶, Yayi He², Caicun Zhou²

Affiliations

¹ Medical College of Soochow University, Suzhou, China.
² Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.
³ Medical School, Tongji University, Shanghai, China.
⁴ Pathology Department, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.
⁵ Anhui No.2 Provincial People's Hospital, Hefei, China.
⁶ Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Shanghai, China.

Abstract

Background: It has been proven that the treatment window of small cell lung cancer (SCLC) is short, so it is vital to find other possible therapeutic targets. CD39 inhibits natural killer (NK) cells and promotes the occurrence and metastasis of tumors. There has been little research about the role of CD39 in SCLC, so we explored the correlation between CD39 and other surface antigens, and its association with survival in SCLC.

Methods: This study included 75 patients with SCLC from Shanghai Pulmonary Hospital. After paraffin embedding and sectioning, immunohistochemistry (IHC) was applied. Then we identify cutoff value for CD39 and other surface antigens based on the analysis of ROC curve in RFS by SPSS. All statistical analyses were based on SPSS and Graphpad Prism8. Chi-square test, Kendall's tau-b correlation analysis, Logistic regression analysis, Kaplan-Meier method, univariate and multivariate Cox regression analysis were conducted. In all analyses, P = 0.05 distinguished whether they had statistical significance.

Results: Of the 75 SCLC patients enrolled in this study, 61.33% positively expressed CD39. A correlation between CD39 and programmed cell death-ligand 1 (PD-L1) (P=0.007), CD3 (P<0.001), CD4 (P<0.001), CD8 (P<0.001), and forkhead box P3 (FOXP3) (P<0.001) on tumor-infiltrating lymphocytes (TILs) was identified by correlation analysis and logistic regression analysis. Based on Kaplan-Meier survival analysis, we found that CD39 affected relapse-free survival (RFS) [negative vs. positive, 95% confidence interval (CI): 0.2765-0.9862, P=0.0390]. SCLC patients with high-expressed CD39 and low-expressed PD-L1 had poor prognosis (P<0.001). Positive expression of CD39 and negative expression of CD3, CD4, CD8, and FOXP3 also indicated shorter RFS (P=0.0409). Univariate and multivariate Cox regression analysis was performed to confirm the factors that influenced RFS.

Conclusions: CD39, programmed cell death-1 (PD-1), and PD-L1 expressed on TILs but not on tumor cells. CD39 has a significant association with PD-L1, CD3, CD4, CD8, and FOXP3 on TILs. The positive expression of CD39 predicts poor prognosis. SCLC patients with low expression of CD39 combined with high expression of PD-L1 or CD3, CD4, CD8, and FOXP3 have a more favorable prognosis.

Keywords: CD39; programmed cell death-1 (PD-1); programmed cell death-ligand 1 (PD-L1); progress-free survival; small cell lung cancer (SCLC); tumor-infiltrating lymphocyte (TIL).