PD-L1和FOXM1在NSCLC中的表达及临床预后的相关性分析

发布时间：2018-05-02 19:43

本文选题：PD-L1 + FOXM1　；参考：《大连医科大学》2017年硕士论文

【摘要】：目的:通过检测PD-L1和FOXM1蛋白在非小细胞肺癌(none small cell lung cancer,NSCLC)组织中的表达情况,分析其表达与患者临床病理参数和预后之间的关系,同时分析二者表达是否具有相关性,进一步了解PD-L1表达水平调控的机制,为探索NSCLC免疫治疗的疗效预测提供理论依据。方法:收集大连医科大学附属第二医院胸外科2014.11-2015.4期间收治的行手术切除且组织学证实为NSCLC的患者石蜡组织标本80例,同时选取癌旁组织20例作为对照,通过免疫组化的方法检测PD-L1和FOXM1蛋白在组织中的表达情况,应用细胞染色着色强度与阳性细胞数量的乘积进行评估。采用SPSS22版对所有数据进行统计学分析,并用卡方检验分析PD-L1和FOXM1蛋白表达与NSCLC患者临床病理资料特征之间的相关性,Kaplan-Meier生存曲线、Log-rank检验进行预后分析,Spearman等级相关分析法分析癌组织中两种蛋白表达的相关性。结果:NSCLC组织中PD-L1表达定位于细胞膜和细胞浆,癌组织中阳性表达率为56.3%(45/80),较癌旁组织30%(6/20)显著升高(χ2=4.412,P0.05);PD-L1表达与肿瘤大小(χ2=7.672,P0.05)、淋巴结转移(χ2=5.261,P0.05)、TNM分期(χ2=11.506,P0.05)、FOXM1表达(χ2=10.173,P0.05)显著相关;与性别、年龄、吸烟状态、病理类型、分化程度均无明显相关性(P0.05)。FOXM1表达定位于细胞核,癌组织中阳性表达率为65%(52/80),较癌旁组织40%(8/20)显著升高(χ2=4.167,P0.05);FOXM1表达与肿瘤组织分化程度(χ2=10.741,P0.05)、淋巴结转移(χ2=7.299,P0.05)、TNM分期(χ2=11.747,P0.05)显著相关;与性别、年龄、是否吸烟、病理类型、肿瘤大小均无明显相关性(P0.05)。Kaplan-Meier单因素生存分析显示PD-L1和FOXM1蛋白表达阳性组无复发生存期(RFS)较阴性组显著降低(log-rank检验结果示χ2=4.238,P0.05;χ2=4.368,P0.05),差异具有统计学意义,提示与预后呈负相关。PD-L1和FOXM1表达在总生存(OS)上无统计学差异(P0.05)。Spearman相关性分析显示NSCLC组织中PD-L1和FOXM1表达呈正相关(R=0.357,P0.01)。结论:1.PD-L1和FOXM1参与NSCLC的发生发展。2.PD-L1和FOXM1在NSCLC的侵袭和转移中发挥作用。3.PD-L1和FOXM1高表达是NSCLC患者预后不良的预测因子。4.在NSCLC组织中可能存在FOXM1对PD-L1的调控作用。
[Abstract]:Objective: to investigate the expression of PD-L1 and FOXM1 in non-small cell lung cancer (NSCLC), and to analyze the relationship between the expression and clinicopathological parameters and prognosis of NSCLC. To further understand the mechanism of PD-L1 expression level regulation, to explore the efficacy of NSCLC immunotherapy prediction provides theoretical basis. Methods: a total of 80 paraffin tissue specimens were collected from thoracic surgery department of the second affiliated Hospital of Dalian Medical University from April to April 2014,2014.The paraffin tissue specimens were obtained from 80 patients with histologically proved NSCLC, and 20 patients with paracancerous tissue were selected as control group. The expression of PD-L1 and FOXM1 in tissues was detected by immunohistochemical method, and the product of staining intensity and the number of positive cells was used to evaluate the expression. Using the SPSS22 version of all the data for statistical analysis, The correlation between the expression of PD-L1 and FOXM1 protein and the clinicopathological features of NSCLC patients was analyzed by chi-square test. Kaplan-Meier survival curve and Log-rank test were used to analyze the prognostic analysis. Spearman rank correlation analysis was used to analyze the correlation between the expression of the two proteins in cancer tissues. Results the expression of PD-L1 was localized in cell membrane and cytoplasm. The positive expression rate of PD-L1 in cancer tissues was 56.33 / 45 / 80, which was significantly higher than that in adjacent tissues (蠂 24.412 P 0.05 P 0.05 P 0.05 P 0.05) (蠂 2 / 7.672P 0.05 and lymph node metastasis (蠂 ~ 25.261) P 0.05 / 0. 05 TNM stage (蠂 ~ 211.506) (蠂 ~ 210.173P 0.05), and it was associated with sex, age, and lymph node metastasis (蠂 ~ 25.261 ~ (11.506) (蠂 ~ (2) 11.506) (蠂 ~ (210.173) P 0.05), and the expression of PD-L1 was significantly correlated with sex, age, and tumor size. There was no significant correlation among smoking status, pathological type and differentiation degree. The expression of P0.05A. FOXM1 was located in the nucleus. The positive expression rate of FOXM1 in cancer tissues was 65 / 52 / 80, which was significantly higher than that in paracancerous tissues (40 / 20) (蠂 ~ 24.167 / P 0.05). The expression of FOXM1 was significantly correlated with the differentiation of tumor tissues (蠂 ~ 2 / 10.741) and lymph node metastasis (蠂 ~ 2 / 7.299P _ 0.05TNM staging (蠂 ~ 2 / 7.299P _ 0.05TNM) (蠂 ~ 2 / 7.299P _ 0.05T _ 0.05), and was significantly correlated with sex, age, smoking, pathological type, sex, age, smoking and pathological type. There was no significant correlation between tumor size and tumor size. Kaplan-Meier single factor survival analysis showed that PD-L1 and FOXM1 protein expression positive group had significantly lower survival time without recurrence than negative group. The results of 蠂 2 + 4. 238% P 0.05 and 蠂 2 + 4. 368% P 0. 05 were significantly lower than those of negative group, and the difference was statistically significant. It was suggested that there was no significant difference in the expression of PD-L1 and FOXM1 in the total survival of NSCLC. The correlation analysis showed that there was a positive correlation between the expression of PD-L1 and FOXM1 in NSCLC tissues. Conclusion: 1. PD-L1 and FOXM1 are involved in the occurrence and development of NSCLC. 2.PD-L1 and FOXM1 play a role in the invasion and metastasis of NSCLC. 3. The high expression of PD-L1 and FOXM1 is the predictor of poor prognosis in NSCLC patients. The regulation of FOXM1 on PD-L1 may exist in NSCLC tissues.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

【参考文献】