原发性肝癌中KRAS及BRAF基因突变检测及临床意义分析

新发传染病电子杂志 ›› 2018, Vol. 3 ›› Issue (1): 37-40.

原发性肝癌中KRAS及BRAF基因突变检测及临床意义分析

邬宇美, 骆子义, 黄华

深圳市第三人民医院,广东深圳 518112

收稿日期:2017-11-16 出版日期:2018-02-28 发布日期:2020-06-29
通讯作者: 骆子义,Email：13501569621@163.com
基金资助:
深圳市科技计划项目（JCYJ20160427153326556）

Detection of KRAS and BRAF gene mutations in primary hepatocellular carcinoma and its clinical significance

WU Yu-mei, LUO Zi-yi, HUANG Hua

The Third People's Hospital of Shenzhen, Guangdong Shenzhen 518112, China

Received:2017-11-16 Online:2018-02-28 Published:2020-06-29

摘要/Abstract

摘要： 目的研究分析KRAS及BRAF基因突变在原发性肝癌中的表达及临床意义,分析其与疾病发展相关性。方法选取2016年1月至2017年5月期间在我院接受诊治的126例肝癌患者作为研究对象,其中原发性肝癌且伴肝外转移者62例（研究组）,病灶局限在肝脏者64例（对照组）。所有患者均于入院接受诊治当天空腹状态下抽取10ml外周血,由血样内游离DNA,应用KRAS/NRAS基因突变的联合检测试剂盒、人类BRAF基因V600E突变的检测试剂盒检测KRAS、BRAF基因突变,对基因突变率、突变临床特征进行分析。结果 126例患者中检出KRAS基因突变者15例,其中伴肝外转移的KRAS基因突变率是24.2%（15/62）,但无肝外转移的突变率是0.0%（0/64）;伴肝外转移患者的KRAS基因突变率显著高于无肝外转移患者的KRAS基因突变率,差异有统计学意义（P<0.05）;提示KRAS基因突变和肝癌伴肝外转移存在显著相关性;126例患者中均无BRAF基因突变检出。结论肝癌患者的KRAS基因出现显著突变,同时肝癌伴肝外转移者的KRAS基因突变率显著增加;无BRAF基因突变检出,或BRAF基因突变率表现较低。

关键词: KRAS基因突变, BRAF基因突变, 原发性肝癌

Abstract: Objective To study the expression and clinical significance of KRAS and BRAF mutations in primary hepatocellular carcinoma (HCC), and analyze their relationship with disease development. Methods 126 cases of HCC patients treated in our hospital from January 2016 to May 2017 were enrolled in this study. Among them, 62 cases of patients with primary HCC accompanied by extrahepatic metastasis (the study group), 64 cases of patients with focal liver lesions (the control group). All patients were drawn on the day of admission for treatment of fasting 10ml peripheral blood samples from the blood free DNA, the application of KRAS / NRAS gene mutation detection kit, human BRAF gene V600E mutation detection kit KRAS, BRAF gene mutations, The gene mutation rate, mutation clinical features were analyzed. Results In 126 patients, KRAS mutation was found in 15 cases. The mutation rate of KRAS gene with extrahepatic metastasis was 24.2% (15/62), but the rate of non-extrahepatic metastasis was 0.0% (0/64). The mutation rate of KRAS gene in patients with extrahepatic metastasis was significantly higher than that in patients without extrahepatic metastasis, the difference was statistically significant (P <0.05). It is suggested that there is a significant correlation between KRAS gene mutation and extrahepatic metastasis of hepatocellular carcinoma. No mutation of BRAF gene was detected in 126 cases. Conclusion There was a significant mutation of KRAS gene in patients with hepatocellular carcinoma, and a significant increase of KRAS gene mutation rate in patients with hepatocellular carcinoma and extrahepatic metastasis. No mutation of BRAF gene was detected or the rate of BRAF gene mutation was lower.

Key words: KRAS gene mutation, BRAF gene mutation, Primary liver cancer

邬宇美, 骆子义, 黄华. 原发性肝癌中KRAS及BRAF基因突变检测及临床意义分析[J]. 新发传染病电子杂志, 2018, 3(1): 37-40.

WU Yu-mei, LUO Zi-yi, HUANG Hua. Detection of KRAS and BRAF gene mutations in primary hepatocellular carcinoma and its clinical significance[J]. Electronic Journal of Emerging Infectious Diseases, 2018, 3(1): 37-40.

参考文献

[1] 张金坤,王燕燕. 原发性肝癌发生机制及其治疗的研究进展[J].中国药房,2015,26(29):4171-4173.
[2] Klein J, Dawson LA, Jiang H, et al.Prospective longitudinal assessment of quality of life for liver cancer patients treated with stereotactic body radiation therapy[J]. Int J Radiation Oncology Biol Physics, 2015, 93(1) : 16-25.
[3] 韩义明,饶兰,丁莉,等.非小细胞肺癌中BRAF V600、EGFR基因突变与临床病理特征的关系[J].临床与实验病理学杂志,2017,33(4):375-378.
[4] 赵鹏,郑加生,张洪海,等. 肝动脉导管化疗栓塞联合 CT 引导精准微波消融治疗原发性肝癌的疗效及影响因素[J]. 中华肿瘤杂志,2016,38(2):138-145.
[5] 中国抗癌协会肝癌专业委员会.原发性肝癌的临床诊断与分期标准[J].中华肝脏病杂志,2001,9(6):324.
[6] 曹丽荣. 肿瘤标志物联合甲胎蛋白检测方法在原发性肝癌患者中的诊断研究[J]. 中国药物与临床,2017,17(6):909-911.
[7] 林晓渊. 血清异常凝血酶原检测在原发性肝癌诊断中的应用研究[J]. 中国社区医师,2017,33(1):102–104.
[8] 康晓艳,屈丽岩,宋霞. BRAF基因与非小细胞肺癌的分子靶向治疗[J].国际肿瘤学杂志,2016,43(8):625-627.
[9] 李淑敏. 血清异常凝血酶原检测对诊断原发性肝癌的应用价值分析[J]. 影像研究与医学应用,2017,1(11):210-211.
[10] Kuncewitch M, Yang W L, Jacob A, et al.Stimulation of Wnt/beta-carenin signaling pathway with Wnt agonist reduces organ injury after hemorrhagic shock[J]. J Trauma Acute Care Surg, 2015, 78(4) : 793-900.
[11] 黎莉,杨卫文,魏涛,等. 乙型肝炎肝硬化并发原发性肝癌的危险因素Logistic分析[J]. 中国老年学杂志,2016,36(7):1653-1654.
[12] 王虎明,巴彩霞,丽敏. 血清肿瘤标志物检测对肝癌及转移患者的临床意义[J]. 标记免疫分析与临床,2016,23(8):881-884.
[13] Choi GH, Shim JH, Kim MJ, et al.Sorafenib alone versus sorafenib combined with transarterial chemoembolization for advanced-stage hepatocellular carcinoma: Results of propensity score analyses[J].Radiology,2013, 269(2): 603-611.
[14] 张小花. 磷脂酰肌醇蛋白聚糖3与甲胎蛋白联合检测对原发性肝癌的诊断价值分析[J]. 世界临床医学,2017,11(5):229,231.
[15] 李藏妥,宋光,曹宏霞,等.血清降钙素原与C-反应蛋白对肝癌介入手术患者感染的监测[J].中华医院感染学杂志,2016,26(5): 994-995,1004.
[16] Allegra CJ, Rumble RB, Hamilton SR, et al.Extended ras gene mutation testing in metastatic colorectal carcinoma to predict response to anti - epidermal growth factor receptor monoclonal antibody therapy : American society of clinical oncology provisional clinical opinion update 2015[J]. J Clin Oncol, 2016, 34(2): 179-185.
[17] 尹小兰,许青. 原发性肝癌中 KRAS 及 BRAF 基因突变及其临床意义[J]. 2016,24(15):2419-2422.
[18] 张晶晶,陆小军,叶奕菁,等.Kras突变基因真核表达载体的构建及在不同肝细胞株中的表达[J].现代生物医学进展,2014,14(1):18-22.
[19] 吕矫洁,孔蕴毅,蔡旭,等.BRAF V600E抗体在检测恶性黑色素瘤BRAF V600E基因突变中的应用价值[J].中华病理学杂志,2017,46(8):548-552.
[20] 彭薇,何剪太,金鑫,等.MiR-30c通过靶向KRAS抑制肝癌细胞系生长侵袭能力的体外研究[J].中国现代医学杂志,2015,25(12):25-29.