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中国非小细胞肺癌患者表皮生长因子受体和KRAS基因突变与预后的相关性

Relationship between EGFR and KRAS mutations and prognosis in Chinese patients with non-small cell lung cancer: a mutation analysis with real-time polymerase chain reaction using scorpion amplification refractory mutation system

摘要:

目的 探讨中国非小细胞肺癌(NSCLC)患者中表皮生长因子受体(EGFR)和KRAS基因突变情况与预后之间的相关性.方法 回顾性分析2009年3月至2010年12月间来自北京协和医院的158例NSCLC患者资料,其中120例采用扩增阻遏突变系统(ARMS)法行EGFR突变检测,104例行KRAS突变检测,分析其EGFR和KRAS突变情况及与预后的相关性.结果 在120例进行EGFR检测的NSCLC患者中,共检测到44例(36.7%)存在EGFR突变,分别为:EGFR外显子19缺失突变(29例,24.2%),EGFR外显子21 L858R(2573T> G)突变(14例,11.7%)和EGFR外显子21L861Q(2582T>A)突变(1例,0.8%).未发现多位点突变.在NSCLC患者群体中,腺癌(P =0.009)、女性(P=0.014)、无吸烟史患者(P=0.001)的突变率比非腺癌、男性、有吸烟史患者的突变率高.在腺癌患者中,无吸烟史患者(P =0.008)和高分化患者(P =0.018)的突变率比有吸烟史患者和低分化患者的突变率高.未发现EGFR突变患者比EGFR野生型患者在预后和EGFR-TKI治疗反应率上存在差别.在104例行KRAS检测的患者中,共检测到9例患者(8.7%)存在KRAS突变,分别为:KRAS Gly12Ala(GGT> GCT)突变(2例)、KRAS Gly12Arg(GGT> CGT)突变(2例)、KRAS Gly12Val(GGT> GTT)突变(2例)和KRAS Gly12Cys(GGT> TGT)突变(4例).其中1例为多位点突变[KRAS Gly12Cys(GGT> TGT)突变和KRAS Gly12Ala(GGT> GCT)突变].未发现临床病理特征与KRAS突变存在相关性.发现KRAS突变患者比KRAS野生型患者预后差(P =0.008).未发现同一患者中同时存在EGFR和KRAS突变.结论 中国NSCLC患者EGFR突变率与性别、吸烟史及病理类型相关,其中腺癌患者突变率与吸烟史及分化程度相关.KRAS突变的NSCLC患者比野生型患者预后更差.

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abstracts:

Objective To investigate the gene mutation of EGFR and KRAS in Chinese patientswith non-small cell lung cancer (NSCLC),and to analyze the relationship between the gene mutations and the clinicopathological features and EGFR-TKI efficiency.Methods EGFR mutation was detected in 120 patients and KRAS mutation in 104 patients with NSCLC in Peking Union Medical College Hospital from March 2009 to December 2010,and the correlation of the gene mutations with the clinicopathological features and EGFR-TKI efficiency was analyzed in the study.Results EGFR mutation was detected in 44 of 120 (36.7%) patients with NSCLC,in which three types of EGFR gene mutations were found:deletion in exon 19,exon 21 L858R (2573T > G) and Exon 21 L861Q (2582T > A) mutations.There were 29(24.2%)patients with EGFR exon 19 deletion,14 (11.7%) patients with EGFR exon 21 L858R mutation and one (0.8%) with EGFR exon 21 L861Q mutation in the patients.All the mutations were single point mutations,and no multiple points mutations detected.EGFR mutation rate of bronchioloalveolar carcinoma and adenocarcinoma were higher than that of non-adenocarcinoma(P =0.009).EGFR mutation rate was higher in female patients or patients without smoking history than male patients or patients with smoking history (P =0.014,P =0.001,respectively) in NSCLC patients.EGFR mutation rate was higher in patients without smoking history or patients with well-differentiated carcinoma than patients with smoking history or patients with moderately-and poorly-differentiated carcinoma (P =0.008,P =0.018,respectively).There was no difference in prognosis and EGFR-TKI treatment response rate between EGFR mutation patients and EGFR wild-type patients.Nine (8.7%) patients with KRAS mutation were detected in 104 NSCLC patients.There were four types of KRAS gene mutations detected:KRAS Gly12Ala (GGT > GCT),KRAS Gly12Arg (GGT > CGT),KRAS Gly12Val (GGT > GTT) and KRAS Gly12Cys (GGT > TGT).There were 4 patients with Cys mutation,2 with Arg mutation,2 with Val mutation and 1 with multiple points mutation of both Cys and Arg in exon 12.No relationship was found between KRAS mutation and clinicopathological feature either in NSCLC or in adenocarcinoma.Prognosis was worse in patients with KRAS mutation than in wild-type patients (P =0.008).No patient with both EGFR and KRAS mutation was detected.Conclusions EGFR mutation rate is related with gender,smoking history and pathological type in NSCLC patients,and is also related with differentiation and smoking history in adenocarcinoma patients.And prognosis is worse in patients with KRAS mutation than that with wild type.

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