非小细胞肺癌驱动基因突变与相关临床指标的相关性分析  

Association of the common driver gene mutations with serum tumor biomarker levels and clinicopathological features in nonsmall cell lung cancer

作　　者：於樱枝 杨朝晖[1] 朱楚梦 曹学全[1] 蔡小波 顾华敏[1] 卢洪胜[1] YU Yingzhi;YANG Zhaohui;ZHU Chumeng;CAO Xuequan;CAI Xiaobo;GU Huamin;LU Hongsheng(Department of Pathology,Taizhou Central Hospital,Taizhou 318000,China;不详)

机构地区：[1]台州市中心医院病理科,318000 [2]台州市中心医院精准医学中心,318000

出　　处：《浙江医学》2023年第14期1479-1485,共7页Zhejiang Medical Journal

基　　金：台州市科技计划项目(1801KY40、22YWA17)。

摘　　要：目的探讨非小细胞肺癌(NSCLC)常见驱动基因突变与血清肿瘤标志物和临床病理特征的关系。方法采用二代测序技术(NGS)检测台州市中心医院收治的120例初诊且未经治疗的NSCLC患者癌组织中表皮生长因子受体(EGFR)、鼠类肉瘤病毒癌基因(KRAS)、鼠类肉瘤滤过性毒菌致癌同源体B1(BRAF)突变、c-ros肉瘤致癌因子-受体酪氨酸激酶(ROS1)融合、间变性淋巴瘤激酶(ALK)、间质上皮转化因子(MET)、人表皮生长因子受体2(HER-2)、肿瘤蛋白p53(TP53)、磷脂酰肌醇-3-激酶催化亚单位α(PIK3CA)等常见驱动基因的突变情况。使用商用化学发光免疫分析试剂盒检测患者血清中癌胚抗原(CEA)、糖类抗原125(CA125)、鳞状细胞癌抗原(SCC)、胃泌素释放前体(Pro-GRP)和细胞角蛋白片段抗原(CYFRA21-1)等肿瘤标志物表达情况。采用Spearman秩相关分析驱动基因单一/多位点突变情况与常规肿瘤标志物及临床特征的相关性,使用AUC分析常规肿瘤标志物与临床特征对NSCLC患者基因突变类型的诊断效能。结果120例NSCLC腺癌组织中具有单一位点突变89例,具有多位点突变31例。其中,EGFR、KRAS、BRAF突变、ROS1融合的发生率相对较高。在NSCLC患者中多位点突变组与单一位点突变组的淋巴结转移情况、临床分期、血清CEA水平、血清CA125水平比较,差异有统计学意义(P<0.05)。在发生淋巴结转移的患者中,多位点突变的发生频率高于单一位点突变的发生频率(P<0.05)。在肺癌晚期(Ⅲ+Ⅳ期)患者中,多位点突变的发生频率高于单一位点突变的发生频率(P<0.01)。高血清CEA水平(≥6.5μg/L)患者多位点突变频率高于低血清CEA水平(<6.5μg/L)的患者(P<0.05),高血清CA125水平(≥35.0 U/mL)的患者多位点突变频率高于低血清CA125水平(<35.0 U/mL)的患者(P<0.05)。驱动基因突变与淋巴结转移和血清CEA、CYFRA21-1水平中度相关,与CA125和临床分期高度相关。淋巴结转�Objective To investigate the relationship of the common driver gene mutations with serum tumor marker levels and clinicopathological features in non-small cell lung cancer(NSCLC).Methods Next-generation sequencing(NGS)technique was used to detect the mutations of common driver genes such as epidermal growth factor receptor(EGFR),kirsten rat sarcoma viral oncogene(KRAS),vrafmurine sarcoma viral oncegene homolog B1(BRAF)variants,ROS proto-oncogene1(ROS1)fusion,anaplastic lymphoma kinase(ALK),mesenchymal-epithelial transition factor(MET),human epidermal growth factor receptor 2(HER-2),tumor protein p53(TP53)and phosphatidylinositol-3-kinase catalytic alpha(PIK3CA)in tissue samples from 120 patients with NSCLC.The serum levels of tumor biomarkers including carcinoma embryonic antigen(CEA),carbohydrate antigen 125(CA125),squamous cell carcinoma antigen(SCC),pro-gastrin releasing peptide(Pro-GRP)and cytokeratin fragments 21-1 antigen(CYFRA21-1)were detected using commercial chemiluminescent immunoassay kits.Spearman test was used to analyze the correlation of single/multi-site co-mutations of driver gene with conventional tumor marker levels and clinicopathological features of NSCLC patients,and the ROC curve was used to analyze the predictive diagnostic performance of conventional tumor markers and clinical features on gene mutation types in NSCLC patients.Results Among 120 cases of NSCLC,88 cases had single mutation site and 32 cases had multiple site mutations.The incidence of EGFR,KRAS,BRAF mutation and ROS1 fusion was relatively high.The multi-site mutation was associated with lymph node metastasis,clinical stage,CEA and CA125 serum levels(P<0.05).The frequency of multi-site mutations in patients with lymph node metastasis,advanced stage,high CEA(≥6.50 ng/mL)or CA125(≥35.00 U/mL)levels were higher than that in patients with single gene mutation(P<0.05).The ROC analysis showed that themulti-site mutations of common driving genes had significant prediction value for lymph node metastasis(P<0.01),clinical stage(P

关 键 词：非小细胞肺癌 二代测序 驱动基因 肿瘤标志物 

分 类 号：R734.2[医药卫生—肿瘤]