乳酸受体GPR81表达水平与晚期肺腺癌吉非替尼获得性耐药的相关性

Association between lactate receptor GPR81 expression levels and gefitinib acquired resistance in advanced lung adenocarcinoma

目的:观察乳酸受体(GPR81)在晚期肺腺癌(LUAD)组织中的表达水平,分析其与临床病理参数及吉非替尼获得性耐药的相关性。方法:通过免疫组织化学方法检测GPR81在65例LUAD患者组织中的表达情况,采用χ^(2)检验分析其与患者临床病理参数的关系。影像学观察65例LUAD患者中有42例出现耐药,免疫组化检测其耐药后病理组织中GPR81的表达水平,采用配对χ^(2)检验分析其与吉非替尼获得性耐药的关系。采用Kaplan-Meier生存分析法分析GPR81表达与患者无进展生存期(PFS)的关系,并采用Cox模型分析多因素与患者PFS的关系。结果:GPR81在LUAD患者肿瘤组织中的表达水平与肿瘤N分期及远处转移正相关(P<0.05)。42例LUAD患者吉非替尼耐药后肿瘤组织中GPR81表达水平高于用药前(P<0.05)。Kaplan-Meier单因素分析结果显示GPR81高表达患者的PFS明显低于GPR81低表达患者(P<0.05),Cox比例风险模型多因素分析结果显示GPR81的表达水平是影响晚期LUAD患者预后的危险因素。结论:GPR81高表达与肿瘤N分期、远处转移及PFS有关,表明其可能促进了LUAD的发生发展;GPR81在LUAD患者吉非替尼耐药后组织中高表达,表明其与吉非替尼靶向治疗耐药密切相关。

Objective:To observe the expression level of lactate receptor(GPR81)in advanced lung adenocarcinoma(LUAD)tissues,and analyze its correlation with clinicopathological parameters and gefitinib acquired resistance.Methods:The expression of GPR81 in the tissues of 65 LUAD patients was detected by immunohistochemistry,and the relationship between GPR81 expression and clinicopathological parameters of patients was analyzed byχ^(2).Radiographically,42 of the 65 LUAD patients were drug-resistant,and the expression level of GPR81 in the pathological tissues after drug resistance was detected by immunohistochemistry,and the relationship between it and gefitinib acquired resistance was analyzed by pairedχ^(2) test.The relationship between GPR81 expression and patient progression-free survival(PFS)was analyzed by Kaplan-Meier survival analysis,and the relationship between multiple factors and patient PFS was analyzed by Cox model.Results:The expression level of GPR81 in tumor tissues of LUAD patients was positively correlated with lymph node metastasis and distant metastasis(P<0.05).The expression level of GPR81 in tumor tissues after gefitinib resistance in 42 patients with LUAD was higher than that before treatment(P<0.05).The results of Kaplan-Meier univariate analysis showed that the PFS of patients with high GPR81 expression was significantly lower than that of patients with low GPR81 expression(P<0.05),and the results of multivariate analysis of Cox proportional hazard model showed that GPR81 expression level was a risk factor affecting the prognosis of patients with advanced LUAD.Conclusion:High expression of GPR81 is associated with lymph node metastasis,distant metastasis and PFS,indicating that it may promote the occurrence and development of LUAD.GPR81 was highly expressed in the tissues of patients with LUAD after gefitinib resistance,indicating that it was closely related to gefitinib targeted therapy resistance.