CAJ | 학술논문

目的检测肺癌患者血清中可溶性程序性死亡配体-1 (sPD-L1)的表达水平,探讨其生物学及临床意义.方法收集2009年6月至2011年3月苏州大学附属第二医院呼吸科收治的肺癌患者81例,男55例,女26例,年龄34 ～ 87岁,平均(65±6)岁.所有肺癌患者均为初诊且经组织或细胞病理学确诊；同时选择88名性别、年龄匹配的健康志愿者作为对照组.采用Western blot方法和酶联免疫吸附方法(ELISA)检测上述人员血清中sPD-L1的表达水平,流式细胞术检测淋巴细胞亚群的变化.结果肺癌患者外周血中sPD-L1平均水平为1.6(0.7～7.8) μg/L,明显高于健康人的0.9(0.4～3.7) μg/L(P＜0.001)；肺癌患者血清中sPD-L1的高表达与有无远处转移及转移程度密切相关(x2=5.636,P＜0.05；x2=4.601,P＜0.05).治疗后达客观缓解的患者,治疗前后血清中sPD-L1的含量分别为2.7(1.6～7.0) μg/L和1.1(0.8～1.7) μg/L(P＜0.01)；病情进展的患者治疗后sPD-L1含量为1.9(1.3～8.5) μg/L,比治疗前的1.4(0.8～2.2) μg/L明显升高(P＜0.01).肺癌患者外周血中T细胞和B细胞亚群也呈异常改变,其中CD8+T细胞数量显著减少(P＜0.05),CD4/CD8比值显著升高(P＜0.05),进一步行双标检测发现T细胞亚群中CD4+ PD-1+及CD8+PD-1+百分率均增高(P＜0.05).结论肺癌患者外周血清中sPD-L1的表达异常增高,且与肺癌的分期、转移和疗效有关,有助于判断肺癌患者的预后,可能成为重要的抗肿瘤靶点或分子标记物.
목적 검측폐암환자혈청중가용성정서성사망배체-1 (sPD-L1)적표체수평,탐토기생물학급림상의의.방법 수집2009년6월지2011년3월소주대학부속제이의원호흡과수치적폐암환자81례,남55례,녀26례,년령34 ～ 87세,평균(65±6)세.소유폐암환자균위초진차경조직혹세포병이학학진；동시선택88명성별、년령필배적건강지원자작위대조조.채용Western blot방법화매련면역흡부방법(ELISA)검측상술인원혈청중sPD-L1적표체수평,류식세포술검측림파세포아군적변화.결과 폐암환자외주혈중sPD-L1평균수평위1.6(0.7～7.8) μg/L,명현고우건강인적0.9(0.4～3.7) μg/L(P＜0.001)；폐암환자혈청중sPD-L1적고표체여유무원처전이급전이정도밀절상관(x2=5.636,P＜0.05；x2=4.601,P＜0.05).치료후체객관완해적환자,치료전후혈청중sPD-L1적함량분별위2.7(1.6～7.0) μg/L화1.1(0.8～1.7) μg/L(P＜0.01)；병정진전적환자치료후sPD-L1함량위1.9(1.3～8.5) μg/L,비치료전적1.4(0.8～2.2) μg/L명현승고(P＜0.01).폐암환자외주혈중T세포화B세포아군야정이상개변,기중CD8+T세포수량현저감소(P＜0.05),CD4/CD8비치현저승고(P＜0.05),진일보행쌍표검측발현T세포아군중CD4+ PD-1+급CD8+PD-1+백분솔균증고(P＜0.05).결론 폐암환자외주혈청중sPD-L1적표체이상증고,차여폐암적분기、전이화료효유관,유조우판단폐암환자적예후,가능성위중요적항종류파점혹분자표기물.
Objective To analyze the expression of soluble programmed death-1 ligand 1 ( sPD-L1 )in the serum of patients with lung cancer and to explore its biological and clinical implications.Methods Fifty-five male and twenty-six female lung cancer patients ages 34 to 87 years ( mean age 65 ± 6 ) were selected from the Department of Respiratory Diseases in The Second Afiliated Hospital of Soochow University from June 2009 to March 2011.All lung cancer patients were newly-diagnosed,treatment-free and confirmed by histopathology or cytopathology. Eight-eight healthy volunteers matching in sex and age from the Healthcare Center of the hospital were also enrolled as controls.The sPD-L1 protein expression in serum was determined by Western blot and self-developed ELISA kit.Fluorescence-labeled monoclonal antibody and cytometry were used to examine changes in lymphocyte subsets in the peripheral blood of lung cancer patients and healthy controls.Results A higher level of sPD-L1 level in the lung cancer patients [ 1.6 (0.7 - 7.8)μg/L] was found compared to the control group [0.9(0.4 -3.7) μg/L] (P ＜ 0.001 ).High expression of sPD-L1 in the lung cancer patients was closely correlated to lymph node metastasis and the extent of distant metastasis ( x2=5.636,P ＜ 0.05 ; x2 =4.601,P ＜ 0.05 ).The sPD-L1 level in lung cancer patients with objective response to treatment ( complete response + partial response) was 2.7 ( 1.6 - 7.0 ) μg/L and 1.1 (0.8 - 1.7) μg/L before and after treatment,respectively ( P ＜ 0.01 ). The level of sPD-L1 with progression disease was 1.9 ( 1.3 - 8.5 μg/L) which was significantly increased compared to the baseline level 1.4 (0.8 - 2.2) μg/L ( P ＜ 0.01 ).Additionally,abnormal changes of T and B lymphocytes and their subsets were found,with a significant decrease of CD8+ T lymphocytes ( P ＜ 0.05 ) and a rise in CD4/CD8 ratio(P ＜ 0.05 ).Further double-labeling study showed increased percentages of CD4+ PD-1 + T lymphocytes and CD8+ PD-1 + T lymphocytes (P ＜ 0.05).Conclusions The elevated expression of sPD-L1 in lung cancer patients was closely related to lung cancer staging,metastasis and clinical response.sPD-L1 may become a predictive marker and an important anti-tumor target in individualized treatment of lung cancer.