CD39: the potential target in small cell lung cancer
Shanhao Chen1, Shengyu Wu2,3, Liping Zhang4
1Medical College of Soochow University, Suzhou, China.
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.
Insights
CD39 expression in small cell lung cancer (SCLC) is linked to poor prognosis. Low CD39 with high PD-L1 or immune cell markers indicates a better outlook for SCLC patients.
Area of Science:
- Oncology
- Immunology
Background:
- Small cell lung cancer (SCLC) has a narrow treatment window, necessitating identification of novel therapeutic targets.
- CD39 is implicated in inhibiting natural killer (NK) cells and promoting tumor progression and metastasis.
- The role of CD39 in SCLC remains underexplored, prompting investigation into its associations with other surface antigens and patient survival.
Purpose of the Study:
- To investigate the correlation between CD39 expression and other surface antigens in SCLC.
- To determine the association between CD39 expression and survival outcomes in SCLC patients.
Main Methods:
- Immunohistochemistry (IHC) was performed on 75 SCLC patient samples.
- Receiver Operating Characteristic (ROC) curve analysis was used to determine cutoff values for CD39 and other antigens.
- Statistical analyses included Chi-square test, Kendall's tau-b correlation, logistic regression, Kaplan-Meier, and Cox regression analyses.
Main Results:
- 61.33% of SCLC patients expressed CD39.
- CD39 showed significant correlations with programmed cell death-ligand 1 (PD-L1), CD3, CD4, CD8, and forkhead box P3 (FOXP3) on tumor-infiltrating lymphocytes (TILs).
- Positive CD39 expression was associated with shorter relapse-free survival (RFS) (P=0.0390). High CD39 and low PD-L1 predicted poor prognosis (P<0.001).
Conclusions:
- CD39, PD-1, and PD-L1 are expressed on TILs in SCLC.
- CD39 expression is significantly associated with PD-L1, CD3, CD4, CD8, and FOXP3 on TILs.
- Positive CD39 expression predicts a poor prognosis, while low CD39 combined with high PD-L1 or immune cell markers suggests a more favorable prognosis.
