原发性肝癌中KRAS及BRAF基因突变及其临床意义

The clinical significance of KRAS and BRAF oncogene mutations in hepatocellular carcinoma

目的:检测原发性肝癌患者血浆中的KRAS与BRAF基因突变机率及特征,研究与疾病进展的相关性及对治疗的意义。方法:收集肝癌患者血液(51例),观察组25例,为肝癌伴肝外转移患者;对照组26例,为病灶局限于肝脏的肝癌患者。所有的患者抽取外周血10ml,从血样中游离DNA,采用人类KRAS/NRAS基因突变联合检测试剂盒及人类BRAF基因V600E突变检测试剂盒分别对KRAS基因和BRAF基因突变进行检测,并分析基因突变机率及与其突变特征。结果:51例肝癌患者中,伴肝外转移患者KRAS基因突变率(24%,6/25)明显高于无肝外转移患者KRAS基因突变率(0%,0/26;P<0.05);肝癌患者中BRAF基因突变率为0%(0/51)。结论:本研究表明肝癌患者KRAS基因会发生明显的突变,且肝癌伴肝外转移患者,KRAS基因突变频率明显增加。未检测出BRAF基因突变或BRAF基因突变率较低。

Objective： To investigate the mutations of KRAS and BRAF genes in patients with hepatocellular carcinoma（ HCC）,and to determine its roles in the development of disease and treatment. Methods： Plasma samples（ 51cases） were collected from HCC patients,including 25 patients with extrahepatic metastasis,and 26 patients without extrahepatic metastasis. 10 ml plasma was collected and DNA was extracted from the plasma samples,and human KRAS / NRAS gene and BRAF V600 E gene mutation detection kits were used to detect KRAS and BRAF gene mutation. Finally analyzing the correlation between gene mutation probability and its clinical and pathological features. Results： The KRAS mutation rates of patients with extrahepatic metastasis（ 24%,6 /25） was much higher than the patients without extrahepatic metastasis（ 0%,0 /26）,and the difference was significant（ P〈0. 05）. No mutation was detected in BRAF gene in hepatocellular carcinoma patients. Conclusion： This study showed that mutation of KRAS gene will be occurred in hepatocellular carcinoma patients,while no mutation was observed in BRAF gene or the mutation ratio of BRAF was low. The KRAS mutation frequency was increased with the increased risk of extrahepatic metastasis.