The Expression Of Programmed Death Ligang-1(PD-l1) In NSCLC And Its Clinical Implications

Objective:To study the expression status of programmed death ligang-1(PD-L1) in human lung cancer tissues and its correlation with clinicopathologic parameters of patients. To investigate the value of PD-L1 as a biomarker of lung cancer.Methods:1. Western-blot analysis was used to explore the expression of PD-L1 in fresh lung cancer tissues, corresponding paraneoplatic tissues(3cm beyond the cancer margin) and normal lung tissues(surgical resected specimens of lung tissue near the cut end).2. Immunohistochemistry staining was performed to study the expression of PD-L1 in 41 cases of NSCLC tissues. 15 cases of benign pulmonary lesion tissues samples were also analyzed as control subjects.The correlation between the expression of PD-L1 in lung cancer tissues and the clinicopathological parameters of the patients were analyzed.3. 19 cases of NSCLC tissues and corresponding paraneoplatic tissues were studied by flow cytometry to analyze the immune cell subsets of CD4+-PD-1, CD8+-PD-1, CD14+ monocytes and CD68+-PD-L1 macrophages.Results:1. Western blot analysis showed the expression of PD-L1 was significantly higher than that in paraneoplatic tissues(102.90±8.66 vs. 46.17±4.85, P<0.05) as well as normal lung tissues(102.90±8.66 vs. 12.75±2.64, P<0.05). The expression of PD-L1 of pericarcinous tissues was remarkably higher than normal lung tissues(46.17±4.85 vs. 12.75±2.64, P<0.05).2.Immunohistochemistry showed that PD-L1 protein in lung cancer tissues was mainly located in cytomembrane and the positive rate of PD-L1 staining was 81.25%(26/32),whereas no expression was observed in benign pulmonary lesion tissues.The程序性死亡配体PD-L1在非小细胞肺癌中的表达及其临床意义英文摘要PD-L1 expression was found to be significantly correlated with clinical TNM staging(?2=4.606,P<0.05),lymphatic metastasis(?2=3.903,P<0.05)and distant metastasis(?2=4.615,P<0.05).However,no significant correlation was found between PD-L1expression with age,sex,smoking status,and tumor size(P>0.05).3. Flow cytometry showed that the proportion of CD4+-PD-1 subset and CD8+-PD-1 subset in NSCLC tissues were higher than in paraneoplatic tissues(59.02±29.35 vs. 43.79±28.17, t=5.735, P<0.001) and(57.41±34.53 vs. 40.24±28.46, t=5.904, P<0.001). The expression of CD14+-PD-L1 subset and CD68+-PD-L1 subset in NSCLC tissues were relatively higher than in paraneoplatic tissues without statistical significance.Conclusion:1. Compared with normal lung tissue and paraneoplatic tissues, PD-L1 was overexpressed in lung cancer, which signifies that PD-L1 played a role in discriminating lung cancer from benign pulmonary lesions; PD-L1 may become a novel biomarker for the diagnosis of lung cancer.2. CD4+-PD-1 and CD8+-PD-1 were overexpressed in lung cancer compared to paraneoplatic tissues, which signifies that PD-L1 may be involved in immune escape of NSCLC.3. The expression status of PD-L1 in lung cancer tissues was also correlated with tumor TNM staging, lymphatic metastasis and distant metastasis, prompting PD-L1 is closely related to the development of lung cancer, and may serve as a useful novel marker of prognosis and target of immunotherapy in lung cancer.