ITGB3在NSCLC中的表达及与PD-L1、病理特征、预后的关系

Expression of ITGB3 in NSCLC and its relationship with PD-L1,pathological features and prognosis

目的分析非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中整合素β3(integrin beta 3,ITGB3)表达与程序性死亡蛋白配体1(programmed death ligand-1,PD-L1)、临床病理特征及预后的关系。方法收集2018年6月至2020年6月于金华市中心医院实施手术治疗的60例NSCLC患者的癌组织及癌旁组织标本,另选取同期行手术治疗的60例肺良性结节标本。检测ITGB3及PD-L1表达,分析ITGB3表达与PD-L1、临床病理特征的关系。通过受试者操作特征曲线(receiver operating characteristic curve,ROC曲线)判断ITGB3预测NSCLC预后的价值。Kaplan-Meier生存曲线分析ITGB3表达与预后的关系。多因素Cox回归分析影响患者预后的相关因素。结果NSCLC组织、癌旁组织及肺良性结节组织的ITGB3 mRNA、PD-L1 mRNA表达水平比较,差异有统计学意义(P<0.05),且其表达水平NSCLC组织>癌旁组织>肺良性结节。Pearson相关性分析显示,在NSCLC组织中ITGB3 mRNA与PD-L1 mRNA表达水平呈正相关(r=0.431,P<0.05)。肿瘤最大直径>5cm、TNM分期Ⅲ+Ⅳ期、低分化的NSCLC组织中ITGB3 mRNA表达水平高于肿瘤最大直径≤5cm、TNM分期Ⅰ+Ⅱ期、中/高分化的NSCLC组织,差异有统计学意义(P<0.05)。ROC曲线显示以2.52为最佳截断值,ITGB3 mRNA表达预测患者死亡的敏感度、特异性及约登指数分别为71.43%、81.25%、0.527,曲线下面积为0.784。ITGB3 mRNA表达≥2.52的NSCLC患者的生存率显著低于ITGB3 mRNA表达<2.52的患者(χ^(2)=15.651,P<0.001)。多因素Cox回归分析结果显示,年龄≥60岁、TNM分期Ⅲ+Ⅳ期、低分化、ITGB3 mRNA表达≥2.52及PD-L1高表达均是影响NSCLC患者预后的危险因素(P<0.05)。结论NSCLC组织中ITGB3高表达,并与PD-L1表达及临床病理特征有关,是影响患者预后的危险因素,具有作为NSCLC生物学标志物和治疗靶点的研究价值。

Objective To analyze the relationship between integrin beta 3(ITGB3)expression and programmed death ligand-1(PD-L1),clinicopathological features and prognosis in non-small cell lung cancer(NSCLC).Methods Cancerous tissue and para-cancerous tissue samples were collected from 60 patients with NSCLC who underwent surgical treatment in Jinhua Central Hospital from June 2018 to June 2020,and another 60 patients with benign pulmonary nodules who underwent surgical treatment during the same period were selected.The expression of ITGB3 and PD-L1 was detected,and the relationship between ITGB3 expression and PD-L1,clinicopathological characteristics was analyzed.Receiver operating characteristic(ROC)curve was used to judge the prognostic value of ITGB3 in NSCLC.Kaplan-Meier survival curve were used to analyze the relationship between ITGB3 expression and prognosis survival.Multivariate Cox regression analysis was performed to analyze the prognostic factors.Results The expression levels of ITGB3 mRNA and PD-L1 mRNA in NSCLC tissues,para-cancerous tissues and benign pulmonary nodules were statistically significant(P<0.05),and the expression levels were NSCLC tissues>para-cancerous tissues>benign pulmonary nodules.Pearson correlation analysis showed that ITGB3 mRNA was positively correlated with PD-L1 mRNA in NSCLC tissues(r=0.431,P<0.05).The expression of ITGB3 mRNA in NSCLC tissues with tumor maximum diameter>5 cm,TNM stageⅢ+Ⅳ,and low differentiation was higher than that in NSCLC tissues with tumor maximum diameter≤5 cm,TNM stageⅠ+Ⅱ,and moderately/highly differentiation,and the differences were statistically significant(P<0.05).ROC curve analysis showed that with 2.52 as the best cut-off value,the sensitivity,specificity and Yoden index of ITGB3 mRNA expression in predicting patient death were 71.43%,81.25%and 0.527,respectively,and area under the curve was 0.784.The survival rate of NSCLC patients with ITGB3 mRNA expression≥2.52 was significantly lower than that of patients with ITGB3 mRNA expression<2.52(χ^(2)=15.651,P<0.001).Multivariate Cox regression analysis showed that age≥60 years old,TNM stageⅢ+Ⅳ,low differentiation,ITGB3 mRNA expression≥2.52 and high PD-L1 expression were all risk factors affecting the prognosis of NSCLC patients(P<0.05).Conclusion ITGB3 is highly expressed in NSCLC tissues,and is related to PD-L1 expression and clinicopathological features,which is a risk factor affecting the prognosis of patients,and has research value as a biological marker and therapeutic target of NSCLC.