Li Mei, Liu Lina, Liu Zhimin, Yue Shichang, Zhou Luming, Zhang Qiuping, Cheng Shihua, Li Rachel W, Smith Paul N, Lu Shen
Laboratory Center, Department of Thoracic Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, Liaoning Province, PR China.
Oncol Rep. 2009 Nov;22(5):1013-20. doi: 10.3892/or_00000529.
KRAS mutation is closely associated to carcinogenesis and prognosis of non-small cell lung cancer (NSCLC). Detection of KRAS mutation can also be used to select NSCLC patients for drug targeting with EGFR tyrosine kinase inhibitors. Data regarding the status of KRAS mutation in mainland China, which would assist in these interventions, is lacking. We have detected KRAS mutation from 103 NSCLC patients in mainland China with high resolution melting analysis (HRM) on LightScanner, and compared this method of detection with sequencing, and found HRM to have greater sensitivity. We found 6 patients (5.8%) with KRAS mutation (3 patients, G12C; 1 patient, G12S; 1 patient, G12V; 1 patient, G13D). KRAS mutation was significantly associated to gender (p=0.027) and pathology types (p=0.000), but not to smoking. The mutation frequency of KRAS in NSCLC patients in mainland China is similar to those in East Asian countries, but lower than those in western countries. However, the spectrum of KRAS mutation in mainland China is similar to those found in the USA. The results also exhibit dependence of KRAS mutation in China on ethnicity. The clinical significance of the spectral pattern of KRAS mutations in TKI resistance or tumorigenesis among patients with NSCLC in mainland China requires further investigation.
KRAS 突变与非小细胞肺癌(NSCLC)的致癌作用及预后密切相关。检测 KRAS 突变还可用于选择适合使用表皮生长因子受体(EGFR)酪氨酸激酶抑制剂进行靶向治疗的 NSCLC 患者。目前缺乏中国大陆地区有助于这些干预措施的 KRAS 突变状态的数据。我们使用 LightScanner 上的高分辨率熔解分析(HRM)技术检测了 103 例中国大陆 NSCLC 患者的 KRAS 突变,并将这种检测方法与测序法进行比较,发现 HRM 的灵敏度更高。我们发现 6 例患者(5.8%)存在 KRAS 突变(3 例为 G12C;1 例为 G12S;1 例为 G12V;1 例为 G13D)。KRAS 突变与性别(p = 0.027)和病理类型(p = 0.000)显著相关,但与吸烟无关。中国大陆 NSCLC 患者中 KRAS 的突变频率与东亚国家相似,但低于西方国家。然而,中国大陆 KRAS 突变的谱型与美国发现的谱型相似。结果还显示中国大陆的 KRAS 突变存在种族依赖性。中国大陆 NSCLC 患者中 KRAS 突变谱型在 TKI 耐药或肿瘤发生中的临床意义需要进一步研究。