B7-H3上调IL-22表达在肺腺癌中的临床意义  

The clinical significance of B7-H3 up-regulating IL-22 expression in lung adenocarcinoma

作　　者：周楠楠 廖海秀 杨英 丁萌 唐伟 陈礼文[1] Zhou Nannan;Liao Haixiu;Yang Ying(Dept of Laboratory,The Second Affiliated Hospital of Anhui Medical University,Hefei 230601)

机构地区：[1]安徽医科大学第二附属医院检验科,合肥230601

出　　处：《安徽医科大学学报》2021年第11期1793-1797,共5页Acta Universitatis Medicinalis Anhui

基　　金：安徽省重点研究与开发计划项目(编号:202004j07020027);安徽省自然科学基金(编号:180805MH229)。

摘　　要：目的探讨协同信号分子B7-H3对白介素22(IL-22)的表达调控及其在肺腺癌中的临床意义。方法采用CRISPR/Cas9技术敲除肺腺癌A549细胞B7-H3基因(A549/KO),同时收集56例肺腺癌患者血清,酶联免疫吸附实验(ELISA)分别检测A549/KO培养上清液和患者血清中的IL-22水平,并检测患者血清中可溶性B7-H3(sB7-H3)含量。分析sB7-H3与IL-22的相关性,建立Logistic回归模型对肺腺癌的危险因素进行预测,并采用受试者工作特征曲线(ROC)探讨sB7-H3、IL-22在肺腺癌诊断中的价值。结果A549/KO细胞上清液IL-22表达水平较野生型A549降低(P<0.05)。肺腺癌患者血清sB7-H3和IL-22的表达水平高于健康对照组(P<0.05)。肺腺癌患者血清sB7-H3和IL-22的表达水平与pT分期、淋巴结是否转移及pTNM分期有关(P<0.05),且sB7-H3和IL-22的表达水平呈正相关(rs=0.316,P<0.05)。通过多因素Logistic回归分析鉴定sB7-H3(OR=1.423,95%CI:1.139~1.778)、IL-22(OR=1.108,95%CI:1.001~1.228)为肺腺癌的危险因素,两者可作为肺腺癌诊断指标。ROC曲线分析表明,IL-22和sB7-H3联合检测(AUC=0.827,95%CI:0.727~0.903)对肺腺癌的诊断性能高于sB7-H3(AUC=0.795,95%CI:0.690~0.877)和IL-22(AUC=0.766,95%CI:0.658~0.853)单项检测。结论B7-H3可通过上调IL-22表达在肺腺癌的发生与发展中发挥作用,联合检测血清sB7-H3和IL-22有助于肺腺癌的诊断与监测。Objective To explore the regulation of the co-signaling molecule B7-H3 on the expression of interleukin 22(IL-22)and its clinical significance in lung adenocarcinoma.Methods CRISPR/Cas9 technology was used to knock out the B7-H3 gene of lung adenocarcinoma A549 cells(A549/KO),meanwhile,serum of 56 patients with lung adenocarcinoma was collected.Enzyme linked immunosorbent assay(ELISA)was used to detect the A549/KO culture supernatation and IL-22 level in serum of the patients and the content of soluble B7-H3(sB7-H3)in serum of the patients.The correlation between sB7-H3 and IL-22 was analyzed,the Logistic regression model was established to predict the risk factors of lung adenocarcinoma,and the value of sB7-H3 and IL-22 in the diagnosis of lung adenocarcinoma was discussed using receiver operating characteristic curve(ROC).Results The expression level of IL-22 in the supernatant of A549/KO cells was significantly lower than that of wild-type A549(P<0.05).The expression levels of sB7-H3 and IL-22 in the serum of patients with lung adenocarcinoma were significantly higher than those of healthy controls(P<0.05).The expression levels of sB7-H3 and IL-22 in the serum of patients with lung adenocarcinoma were related to pT stage,lymph node metastasis and pTNM stage(all P<0.05),and the expression levels of sB7-H3 and IL-22 were positively correlated(rs=0.316,P<0.05).sB7-H3(OR=1.423,95%CI:1.139-1.778)and IL-22(OR=1.108,95%CI:1.001-1.228)were selected as a predictors of lung adenocarcinoma through multivariate Logistic regression analysis.As a diagnostic indicator of lung adenocarcinoma.ROC curve analysis showed that the combined detection of IL-22 and sB7-H3(AUC=0.827,95%CI:0.727-0.903)was better than the detection of sB7-H3 alone(AUC=0.795,95%CI:0.690-0.877)and IL-22 was tested alone(AUC=0.766,95%CI:0.658-0.853).Conclusion B7-H3 can play a role in the occurrence and development of lung adenocarcinoma by up-regulating IL-22 expression.Combined detection of serum sB7-H3 and IL-22 is helpful for the diagnosis and monitori

关 键 词：肺腺癌 B7-H3 IL-22 A549细胞株 

分 类 号：R734.2[医药卫生—肿瘤]