高通量测序检测晚期肺腺癌患者EGFR基因结果与临床的相关性

Relationship between high throughput sequencing for detection of EGFR gene results and clinical features in patients with advanced lung adenocarcinoma

目的研究晚期肺腺癌患者EGFR基因检测结果与临床的相关性。方法对53例晚期肺腺癌患者的石蜡组织标本或血清标本，采用高通量基因检测技术，统计分析基因突变情况及其与临床的相关性。结果53例肺腺癌患者中，检测到EGFR基因突变25例，其中18exon突变0例，19exon突变13例（52.0%），20exon突变1例（4.0%），21exon突变11例（44.0%）；女性患者突变11例，突变率为69.7%，高于男性患者的突变率（38.9%），差异有统计学意义（χ2＝5.801，P＝0.006）；吸烟患者40例，发生突变15例，突变率为37.5%，高于非吸烟患者的突变率（30.8%），差异有统计学意义（χ2＝2.013，P＝0.024）。从石蜡组织切片中检测的突变率为40%，高于血清检测的突变率（10%），差异有统计学意义（χ2＝4.935，P＝0.007）。25例基因突变患者，19exon、21exon的突变丰度表达量分别为1.0850±0.4228、0.9650±0.3285，两组比较差异未见统计学意义。吉非替尼治疗3个月后，根据实体瘤疗效评价标准评价疗效，完全缓解（CR）3例（12%），缓解（PR）17例（68%），稳定（SD）4例（16%），进展（PD）1例（4%）。根据疗效回顾突变丰度表达量分别为3.6400±0.6288、0.9458±0.2403、0.2725±0.0439，四组比较差异有统计学意义（F＝59.508，P＝0.0014），CR组较PR组、SD组，突变丰度显著升高（LSD-t＝6.370，P＝0.0014；LSD-t＝4.760，P＝0.0004），PR组较SD组突变丰度也显著升高（LSD-t＝1.578，P＝0.1369）。EGFR基因突变常见的不良反应为皮疹和腹泻，皮疹发生率为52%，腹泻发生率为24%，与其他不良反应发生率比较差异有统计学意义（χ2＝2.762，P＝0.048）。结论不吸烟的女性肺腺癌患者容易发生EGFR基因突变，而且突变率达到40%，主要集中在19exonDelK746-752和21exonL858R；吉非替尼对EGFR突变型的肺腺癌患者预后较好；常见的不良反应为皮疹和腹泻。

ObjectiveTo study the relationship between detection of EGFR gene results and clinical features in patients with advanced lung adenocarcinoma.MethodsThe paraffin embedded tissues or serum samples of the 53 patients with advanced lung adenocarcinoma were analyzed by high-throughput gene detection, the gene mutation and its correlation with clinic were collected and analyzed.ResultsAmong the 53 patients with lung adenocarcinoma, 25 cases of EGFR gene mutation was detected, 18exon mutation in 0 case, 19exon mutation in 13 cases （52%）, 20exon mutation in 1 case （4%）, 21exon mutation in 11 cases （44%）; 11 cases of female patients with mutations, the mutation rate was 52.9%, which was higher than that of male patients（38.9%, χ2=5.801, P=0.006）. There were 40 smokers, mutation of 15 cases, the mutation rate was 37.5%, which was higher than that of non-smokers （30.8%, χ2=2.013, P=0.024）. The mutation rate detected from paraffin embedded tissues was 40%, which was higher than the mutation detection rate of the serum（10%, χ2=4.935, P=0.007）. Among the 25 patients with gene mutation, the 21exon and 19exon mutation abundance expression levels were 1.0850±0.4228, 0.9650±0.3285, the two groups had no significant difference （P〉0.05）. After 3 months of gefitinib treatment, according to the evaluation of therapeutic effect solid carcinoma, CR in 3 cases （12%）, PR in 17 cases （68%）, SD in 4 cases（16%）, PD in 1 case（4%）. Reviewed the mutation abundances based on curative effect, mutation was found in abundance average expression were 3.6400±0.6288, 0.9458±0.2403, 0.2725±0.0439, the difference among the four groups was significally different （F=59.508, P=0.0014）, CR group compared with PR group, SD group, mutation abundance increased significantly （LSD-t=6.370, P=0.0014; LSD-t=4.760, P=0.0004）, PR group compared with SD group, the mutation abundance increased significantly （LSD-t=1.578, P=0.1369）. The common adverse reactions of EGFR gene mutation were rash and diarrhea, the incidence of rash rate was 52%, and the incidence of diarrhea was 24%, there was significant difference compared with other adverse reactions （χ2=2.762, P=0.048）.ConclusionsFemale patients with lung adenocarcinoma without smoking habit prone to have EGFR gene mutations, and the mutation rate reaches 40%, mainly concentrates in the 19exonDelK746-752 and 21exonL858R; gefitinib on EGFR mutant lung adenocarcinoma patients with good prognosis; the common adverse reactions are rash and diarrhea.