非小细胞肺癌血浆EGFR突变与肿瘤标志物水平的关系

Relationship between plasma EGFR mutation and serum levels of tumor markers in non-small cell lung cancer

目的探讨非小细胞肺癌外周血游离DNA样本EGFR突变率与临床基线特征和血清肿瘤标志物表达水平的关系。方法收集本院确诊为非小细胞肺癌166例。利用PCR和变性高效液相色谱法分析EGFR19和21外显子突变。其中89例同时利用多肿瘤标志物蛋白芯片检测系统检测癌胚抗原(CEA)、糖类抗原125(CA125)、糖类抗原153(CA153)等血清肿瘤标志物,分析突变率与临床基线特征和肿瘤标志物表达水平的关系。结果 166例非小细胞肺癌中,EGFR总突变率19.9%。女性突变率显著高于男性(P=0.037)。腺癌突变率高于其他组织学类型,但未达到显著水平(P=0.096)。CEA、CA153中高表达患者EGFR突变率显著高于低表达者(P=0.048,P=0.017),CA199高表达患者仅有高于中低表达者的趋势(P=0.093)。多变量Logistic分析表明,组织学类型为腺癌,CA153、CEA中、高表达与EGFR突变率相关。结论对于晚期非小细胞肺癌,血浆EGFR突变率与血清肿瘤标志物表达水平明显相关。其标志物水平可作为进一步判断EGFR突变优势群体的因素。

Objective To investigate the relationship of epidermal growth mutation in plasma free DNA with clinical characteristics of baseline as well as serum markers in patients with advanced non-small cell lung cancer （NSCLC）. Methods factor receptor （EGFR） expression levels of tumor One hundred and sixty-six patients with pathologically confirmed NSCLC hospitalized in our department from June 2011 to June 2012 were enrolled in this study. Their clinical data and peripheral blood samples were collected. PCR and denaturing high-performance liquid chromatography （DHPLC） were performed to detect EGFR mutations in exons 19 and 21 in the free DNA from the 166 samples of peripheral blood. The serum levels of 12 tumor makers, such as carcinoembryonic antigen （CEA）, carbohydrate antigen （CA） 125, CA153 and so on, were analyzed with multi-tumor markers protein biochip detective system in 89 patients simultaneously. The relationships of EGFR mutation with the patients＇ clinical characteristics at baseline and with corresponding serum levels of tumor makers were analyzed. Results The total mutation rate of EGFR was 19.9% in 166 NSCLC patients, with that in females significantly higher than that in males （P = 0. 037）. Though the rate was higher in adenocarci- noma than the other histological types, no significant difference was seen among them （ P = 0. 096）. The muta- tion rate was significantly higher in the patients with moderate and high serum levels of CEA and CA153 than those with mild expression levels （P =0.048, P =0.017）. However, the rate was also high in those with high expression of CA199 than those with moderate and mild expression though without significant difference （P = 0. 093）. Multivariable Logistic regression showed that adenocarcinoma, and moderate and high expression of CEA and CA153 were significantly correlated with EGFR mutation. Conclusion The mutation rate of EGFR issignificantly related with the serum levels of tumor markers in late NSCLC, and the serum levels can be a poten- tial indicator to determine the EGFR mutation.