中国非小细胞肺癌患者K-Ras和EGFR基因突变与临床病理特征的关系

目的 探讨中国非小细胞肺癌（NSCLC）患者中K-Ras和表皮生长因子受体（EGFR）基因突变情况及其与临床病理特征的关系。方法 回顾性分析2011年7月至2013年8月广州医科大学附属第一医院收治的381例NSCLC患者的临床病理特征，并应用扩增突变阻滞系统（ARMS）检测其癌组织中EGFR基因18、19、20、21外显子共21个点突变和K-Ras基因12、13密码子共6个点突变，分析其突变情况及与临床病理特征的相关性。结果 21例（5.5％）存在K-Ras基因突变，其中20例12密码子，1例13密码子Asp突变；146例（38.3％）存在EGFR突变，其中4例18外显子突变（G719S），52例19号外显子序列缺失突变，3例20外显子序列缺失突变，85例21外显子突变（81例L858R，4例L861Q），2例双突变。男性患者K-Ras基因突变率高于女性患者，差异有统计学意义（6.8％ vs. 2.5％， P=0.018）。EGFR基因突变与性别、吸烟史、临床分期、全身转移、病理类型均有关（P＜0.05）。二分类Logistic回归分析显示，病理类型和性别与EGFR基因突变密切相关。结论 中国NSCLC患者中EGFR突变常见，该突变与腺癌有关；K-Ras基因突变率较低，多见于男性，其他相关因素尚需进一步研究。

Relationship between the mutations of K-Ras and EGFR gene and the clinicopathological features of nonsmall cell lung cancer

Objective To investigate the relationship between the mutations of K-Ras and epidermal growth factor receptor （EGFR） gene and K-Ras gene and clinicopathological features in Chinese patients with non-small cell lung cancer（NSCLC）. Methods From July 2011 to August 2013, 381 cases of NSCLC patients with both EGFR and K-Ras mutations tested in the First Affiliated Hospital of Guangzhou Medical University were retrospectively enrolled in the study. All pathological specimens were tested for twentyone mutations in EGFR 18-21 exon and six mutations in K-Ras 12,13 codon by amplification refractory mutation system（ARMS）. The clinicopathological features of patients were analyzed according to the mutation status of EGFR and K-Ras. Results Gene mutation of K-Ras was tested in 21 cases, including 20 cases 12 codon mutation and 1 case 13 codon mutation. Gene mutation of EGFR was tested in 146 cases, including 4 cases of 18 exon G719S mutation, 52 cases of 19 exon delection mutation, 3 cases of 20 exon delection mutation, 85 cases of 21 exon mutation （81 cases of L858R and 4 case of L861Q） and two dual gene mutation. K-Ras mutation was more frequently happened in male patients than in female patients （6.8% vs. 2. 5%, P = 0.018）. EGFR mutations were related with gender, smoking history, TNM stage, systemic metastases and pathological type（P〈0.05）. Binary Logistic regression shown that pathological type and gender were closely related to EGFR mutation（P〈0.05）. Conclusion EGFR mutation was common in Chinese patients with NSCLC, and was related to adenocarcinoma. However, K-Ras mutation was rare and more commonly happened in male patients with NSCLC. More studies should be conducted to investigate the relationship between clinical features and EGFR and K-Ras mutation.