血浆sPD-L1与非小细胞肺癌患者疗效及预后的相关性研究

发布时间：2018-04-14 03:09

本文选题：非小细胞肺癌 + 可溶性程序性死亡配体1　；参考：《山西医科大学》2017年硕士论文

【摘要】：目的:观察可溶性程序性死亡配体1(s PD-L1)在非小细胞肺癌患者血浆中的表达水平及其与临床特征的相关性。观察治疗前后s PD-L1动态变化与临床疗效及EGFR基因状态是否相关。方法:收集2014年4月至2017年1月,山西省肿瘤医院收治的经病理学检查确诊的初治非小细胞肺癌176例,肺部良性病变12例,选取本院体检中心的73例健康体检者作为对照组。用酶联免疫吸附法检测各组血浆s PD-L1的表达并动态监测非小细胞肺癌组治疗前、后的表达水平,用ARMS法检测肺癌患者EGFR基因状态,观察血浆s PD-L1与疗效及EGFR的相关性。对患者进行随访,分析s PD-L1表达水平与预后的关系。结果:非小细胞肺癌组血浆s PD-L1表达明显高于肺部良性病变组和健康对照组(分别为3.18±2.04ng/ml、1.36±1.02ng/ml和1.67±0.38ng/ml,P0.05);s PD-L1表达与非小细胞肺癌患者的性别、年龄、吸烟状况、病理类型、肿瘤分期及转移情况无明显相关性(P0.05)。治疗2、4周期后,疾病得到控制的患者,s PD-L1表达水平较治疗前均降低(分别为1.22ng/ml vs 1.09ng/ml;1.61ng/ml vs 0.87ng/ml,P0.05);疾病进展组较疾病控制组s PD-L1表达高,但差异无统计学意义(分别为1.23ng/ml vs 1.09ng/ml;1.17ng/ml vs0.87ng/ml,P0.05)。EGFR突变型(19缺失突变、21点突变)患者s PD-L1表达水平明显高于野生型(4.08±2.29ng/ml vs 2.71±1.74ng/ml,P=0.001);EGFR突变患者治疗后的s PD-L1水平较治疗前降低(2.46ng/ml vs 1.69ng/ml,P=0.028),而野生型治疗前后s PD-L1表达无明显差异;EGFR突变患者,使用EGFR-TKI治疗后s PD-L1水平明显下降(2.61ng/ml vs 1.19ng/ml,P=0.023),而化疗患者治疗前后s PD-L1水平的差异无统计学意义(P=0.622)。s PD-L1低表达组较高表达组的中位生存时间长(28个月vs 12个月,P0.001),而中位无疾病进展时间无明显差异(9个月vs10个月,P=0.184)。结论:非小细肺癌患者血浆s PD-L1表达高于健康人群和肺部良性病变人群,s PD-L1的动态变化与临床疗效有关,EGFR突变状态影响非小细胞肺癌患者血浆s PD-L1的表达水平,血浆s PD-L1高表达的患者可能预后较差,提示s PD-L1可能作为非小细胞肺癌患者预测疗效及预后的分子标志物。
[Abstract]:Aim: to investigate the expression level of soluble programmed death ligand 1s PD-L 1 in plasma of patients with non small cell lung cancer (NSCLC) and its correlation with clinical features.To observe whether the dynamic changes of s PD-L1 were correlated with clinical efficacy and EGFR gene status before and after treatment.Methods: from April 2014 to January 2017, 176 cases of newly treated non-small cell lung cancer (NSCLC) and 12 cases of pulmonary benign lesions (NSCLC) were collected from Shanxi Cancer Hospital, and 73 healthy controls were selected as control group.The expression of plasma s PD-L1 was detected by enzyme linked immunosorbent assay (Elisa), and the expression of s PD-L1 was dynamically monitored before and after treatment in non-small cell lung cancer group. The status of EGFR gene in lung cancer patients was detected by ARMS method. The correlation between plasma s PD-L1 and therapeutic effect and EGFR was observed.Patients were followed up to analyze the relationship between the expression of s PD-L1 and prognosis.Results: the expression of plasma s PD-L1 in non-small cell lung cancer group was significantly higher than that in benign lung disease group and healthy control group (3.18 卤2.04ng / ml 1.36 卤1.02ng/ml and 1.67 卤0.38ng / ml / ml P 0.05N PD-L1, respectively) and sex, age, smoking status, pathological type of NSCLC patients.There was no significant correlation between tumor staging and metastasis (P 0.05).After 2 cycles of treatment, the expression of s PD-L1 in patients with disease control was significantly lower than that before treatment (1.22ng/ml vs 1.09ng / ml vs 0.87ng / ml vs 0.87ng / ml P 0.05), and the expression of s PD-L1 in disease progression group was higher than that in disease control group (P < 0.05).However, there was no significant difference in the expression of s PD-L1 in patients with 1.23ng/ml vs 1.09ng / ml vs 1.17ng / ml vs 0.87ng / ml vs 0.87ng / ml / ml respectively. The expression of s PD-L1 was significantly higher in patients with wild type (4.08 卤2.29ng/ml vs 2.71 卤1.74 ng / ml vs 2.71 卤1.74 ng / ml vs 2.71 卤1.74 ng / ml vs 1.69 ng / ml vs 1.69 ng / ml vs 1.69 ng / ml vs 1.69 ng / ml respectively) after treatment, and the expression level of s PD-L1 was significantly lower than that before treatment (2.46 ng / ml vs 1.69 ng / ml P 0.028).There was no significant difference in the expression of s PD-L1 before and after wild-type therapy in patients with EGFR mutation.After treatment with EGFR-TKI, the level of s PD-L1 decreased significantly (2.61 ng / ml vs 1.19 ng / ml vs 1.19 ng / ml). There was no significant difference in the level of s PD-L1 before and after chemotherapy. The median survival time of the high expression group (28 months vs 12 months, P 0.001) was longer than that of the low expression group (28 months vs 12 months, P 0.001), while there was no significant difference in the level of s PD-L1 before and after chemotherapy treatment in the low expression group (28 months vs 12 months, P 0.001).There was no significant difference in the time of disease progression (9 months vs10 per month).Conclusion: the dynamic changes of plasma s PD-L1 expression in patients with non-small lung cancer are higher than those in healthy and benign lung lesions. The clinical efficacy is related to the effect of the mutation state of PD-L1 on the expression of s PD-L1 in plasma of patients with non-small cell lung cancer.The prognosis of patients with high expression of plasma s PD-L1 may be poor, which suggests that s PD-L1 may be a molecular marker for predicting curative effect and prognosis in patients with non small cell lung cancer (NSCLC).
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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