發(fā)布時間：2018-04-14 03:09

  本文選題：非小細胞肺癌 + 可溶性程序性死亡配體1��； 參考：《山西醫(yī)科大學》2017年碩士論文

【摘要】：目的:觀察可溶性程序性死亡配體1(s PD-L1)在非小細胞肺癌患者血漿中的表達水平及其與臨床特征的相關性。觀察治療前后s PD-L1動態(tài)變化與臨床療效及EGFR基因狀態(tài)是否相關。方法:收集2014年4月至2017年1月,山西省腫瘤醫(yī)院收治的經病理學檢查確診的初治非小細胞肺癌176例,肺部良性病變12例,選取本院體檢中心的73例健康體檢者作為對照組。用酶聯免疫吸附法檢測各組血漿s PD-L1的表達并動態(tài)監(jiān)測非小細胞肺癌組治療前、后的表達水平,用ARMS法檢測肺癌患者EGFR基因狀態(tài),觀察血漿s PD-L1與療效及EGFR的相關性。對患者進行隨訪,分析s PD-L1表達水平與預后的關系。結果:非小細胞肺癌組血漿s PD-L1表達明顯高于肺部良性病變組和健康對照組(分別為3.18±2.04ng/ml、1.36±1.02ng/ml和1.67±0.38ng/ml,P0.05);s PD-L1表達與非小細胞肺癌患者的性別、年齡、吸煙狀況、病理類型、腫瘤分期及轉移情況無明顯相關性(P0.05)。治療2、4周期后,疾病得到控制的患者,s PD-L1表達水平較治療前均降低(分別為1.22ng/ml vs 1.09ng/ml;1.61ng/ml vs 0.87ng/ml,P0.05);疾病進展組較疾病控制組s PD-L1表達高,但差異無統(tǒng)計學意義(分別為1.23ng/ml vs 1.09ng/ml;1.17ng/ml vs0.87ng/ml,P0.05)。EGFR突變型(19缺失突變、21點突變)患者s PD-L1表達水平明顯高于野生型(4.08±2.29ng/ml vs 2.71±1.74ng/ml,P=0.001);EGFR突變患者治療后的s PD-L1水平較治療前降低(2.46ng/ml vs 1.69ng/ml,P=0.028),而野生型治療前后s PD-L1表達無明顯差異;EGFR突變患者,使用EGFR-TKI治療后s PD-L1水平明顯下降(2.61ng/ml vs 1.19ng/ml,P=0.023),而化療患者治療前后s PD-L1水平的差異無統(tǒng)計學意義(P=0.622)。s PD-L1低表達組較高表達組的中位生存時間長(28個月vs 12個月,P0.001),而中位無疾病進展時間無明顯差異(9個月vs10個月,P=0.184)。結論:非小細肺癌患者血漿s PD-L1表達高于健康人群和肺部良性病變人群,s PD-L1的動態(tài)變化與臨床療效有關,EGFR突變狀態(tài)影響非小細胞肺癌患者血漿s PD-L1的表達水平,血漿s PD-L1高表達的患者可能預后較差,提示s PD-L1可能作為非小細胞肺癌患者預測療效及預后的分子標志物。
[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 鹵2.04ng / ml 1.36 鹵1.02ng/ml and 1.67 鹵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 鹵2.29ng/ml vs 2.71 鹵1.74 ng / ml vs 2.71 鹵1.74 ng / ml vs 2.71 鹵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).
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R734.2

【參考文獻】

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1 龐盼;朱sソ，

本文編號：1747435