胸腔积液在肺腺癌基因检测中的应用研究

A study of pleural effusion in genomic detection of lung adenocarcinoma

目的探讨采用肺腺癌患者的胸腔积液进行基因检测结果的可靠性,评估胸腔积液上清在肺腺癌基因检测中的临床应用价值。方法纳入2015年2月至2019年12月经病理确诊为肺腺癌的患者145例,其中来自于北京大学肿瘤医院129例,北京市房山区第一医16例。对其胸腔积液上清样本55例、血浆样本52例、肿瘤组织样本48例,进行常见的1021个肿瘤相关基因的靶向高通量测序,比较胸腔积液上清与肿瘤组织、血浆的基因突变检出情况。结果胸腔积液上清肿瘤相关基因的突变检出率为100.00%,中位最大体细胞等位基因频率为16.40%,基因拷贝数变异检出率为45.45%,与肿瘤组织样本(分别为95.56%、26.55%和45.83%)比较,均差异无统计学意义(均P>0.05);与血浆(分别为90.38%、2.50%和9.62%)比较,差异均有统计学意义(均P<0.05)。在与用药相关的驱动基因中,胸腔积液上清、肿瘤组织和血浆的表皮生长因子受体(EGFR)突变检出率分别为61.82%、58.33%和38.46%,胸腔积液上清的EGFR突变检出率与肿瘤组织差异无统计学意义(P>0.05),但高于血浆(P<0.05)。结论胸腔积液上清在检测基因突变方面具有很高的可靠性和有效性。当肺腺癌患者在临床上难以获取肿瘤组织时,可作为替代样本用于基因检测。

Objective To investigate the reliability of gene detection results using pleural effusion from patients with lung adenocarcinoma,and evaluate the clinical application value of pleural effusion supernatant in gene detection of lung adenocarcinoma.Methods A total of 145 patients with lung adenocarcinoma pathologically confirmed from February 2015 to December 2019 were included,including 129 patients from Peking University Cancer Hospital&Institute and 16 patients from the First Hospital of Fangshan District.In this study,55 pleural effusion supernatant samples,52 plasma samples,and 48 tumor tissue samples were selected to targeted next-generation sequencing(NGS)of 1,021 cancer-related genes,and the ability of gene detection of pleural effusion supernatant,tumor tissue,and plasma were compared.Results The mutation rate of pleural effusion supernatant was 100.00%,the median maximum somatic allele frequency(MSAF)was 16.40%,and the chromosomal copy number detection(CNV)was 45.45%,showed no statistically significant difference compared with the tumor tissue samples(95.56%,26.55%and 45.83%,respectively,P>0.05);However,it showed many advantages compared with plasma samples(90.38%,2.50%and 9.62%).Among the drug-related driver genes,the percentage of EGFR mutation carrier in pleural effusion supernatant,tumor tissue and plasma were 61.82%,58.33%and 38.46%respectively,the percentagein pleural effusion was higher than that in plasma(P<0.05),but had no statistical difference compared with the tissue(P>0.05).Conclusions Pleural effusion supernatant has high reliability and effectiveness in detecting gene mutation.When lung adenocarcinoma patients are difficult to obtain tumor tissue clinically,it can be used as a substitute sample for genetic testing.