Detection of K-ras Gene Mutations in Peripheral Blood Free DNA in Patients with Non-Small Cell Lung Cancer_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

GaoHang , YinJun ,  BaoYong

Department of Respiratory Medicine, The Third People's Hospital of Chengdu, Chengdu, Sichuan, 610031, China;

Corresponding author：

BaoYong, Email: byong65@163.com

Keywords：

Non-small cell lung cancer; Peripheral blood; K-ras gene mutation

DOI：

10.7507/1671-6205.2016107

Video：

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Objective To investigate the clinical significancy of K-ras gene mutation in peripheral blood free DNA in patients with non-small cell lung cancer (NSCLC). Methods A total of 242 patients pathologically diagnosed with NSCLC in the Third People's Hospital of Chengdu were recruited between January 2013 and August 2015. Both tumor tissues and peripheral blood free DNA were collected for detection of K-ras gene mutation by mutant-enriched liquidchip technology. The detection rate was compared between these two kinds of samples. Results In tumor tissues, the K-ras gene mutation was detected in 12 cases with a positive rate of 4.96%. While in peripheral blood samples, the K-ras gene mutation was detected in 10 cases with a positive rate of 4.13%. The detection yield of K-ras gene mutation in peripheral blood had a good consistency with that of lung cancer tissues (Kappa value=0.81). Conclusion K-ras in peripheral blood plasma free DNA can be a surrogate marker for tumor tissues' K-ras gene mutation in screening patients with NSCLC.

Citation： Gao Hang, Yin Jun, Bao Yong. Detection of K-ras Gene Mutations in Peripheral Blood Free DNA in Patients with Non-Small Cell Lung Cancer. Chinese Journal of Respiratory and Critical Care Medicine, 2016, 15(5): 458-460. doi: 10.7507/1671-6205.2016107 Copy

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3.	Lynch TJ, Bell DW, Scrdella R, et al.Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small cell lung cancer to gefitinib.N Engl J Med, 2004, 350:2129-2139.
4.	杨帆, 陈克终, 刘宏伟, 等.K-ras突变导致肺癌细胞对表皮生长因子受体抑制剂耐药的机制.中华试验外科杂志, 2011, 28:1232-1233.
5.	Han SW, Kim TY, Jeon YK, et al.Optimization of patient selection for gefitinib in non-small cell lung cancer by combined analysis of epidermal growth factor receptor mutation, K-ras mutation, and Akt phosphorylation.Clin Cancer Res, 2006, 12:2538-2544.
6.	Massarelli E, Varella-Garcia M, Tang X, et al. KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer.Clin Cancer Res, 2007, 13:2890-2896.
7.	Mao C, Qiu LX, Liao RY, et al. KRAS mutations and resistance to EGFR-TKIs treatment in patients with non-small cell lung cancer:a meta-analysis of 22 studies. Lung Cancer, 2010, 69:272-278.
8.	Marks JL, Broderock S, Zhou Q, et al.Prognostic and therapeutic implications of EGFR and KRAS mutations in respected lung adenocarcinoma.J Thorac Oncol, 2008, 3:111-116.
9.	Wu CC, Hsu HY, Liu HP, et al.Reversed mutation rates of KRAS and EGFR genes in adenocarcinoma of the lung in Taiwan and their implications.Cancer, 2008, 113:3199-3208.
10.	张海萍, 付莉, 陈培琼, 等.特异引物双扩增即时PCR与传统测序法检测肠癌、肺癌患者K-ras基因突变的比较.中华病理学杂志, 2010, 39:757-761.
11.	罗炜, 王慧, 徐韫健, 等.非小细胞肺癌患者KRAS基因突变情况分析.广东医学, 2014, 35:2025-2028.
12.	张卉, 杨新杰, 秦娜, 等.肺腺癌EGFR与KRAS基因突变状态分析.中国肺癌杂志, 2015, 18:686-690.
13.	张卉, 杨新杰, 秦娜, 等.肺鳞癌EGFR与KRAS基因突变状态分析.中国肺癌杂志, 2015, 18:621-625.
14.	衣素琴, 庄园, 朱卫东, 等.非小细胞肺癌中KRAS基因突变分析.中华临床医师杂志(电子版), 2013, 7:9111-9115.
15.	许春伟, 张立英, 吴永芳, 等.非小细胞肺癌患者外周血与组织中K-ras基因突变的研究.贵州医药, 2015, 39:1-3.
16.	Wu S, Zhu Z, He J, et al.A novel mutant-enriched liquidchip technology for the qualitative detection of somatic mutations in KRAS gene from both serum and tissue samples.Clin Chem Lab Med, 2010, 48:1103-1106.

1. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CACancer J Clin, 2016, 66:115-132.
2. Paez JG, Janne PA, Lee JC, et al.EGFR mutations in lung cancer:correlation with clinical response to gefitinib therapy.Science, 2004, 304:1497-1500.
3. Lynch TJ, Bell DW, Scrdella R, et al.Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small cell lung cancer to gefitinib.N Engl J Med, 2004, 350:2129-2139.
4. 杨帆, 陈克终, 刘宏伟, 等.K-ras突变导致肺癌细胞对表皮生长因子受体抑制剂耐药的机制.中华试验外科杂志, 2011, 28:1232-1233.
5. Han SW, Kim TY, Jeon YK, et al.Optimization of patient selection for gefitinib in non-small cell lung cancer by combined analysis of epidermal growth factor receptor mutation, K-ras mutation, and Akt phosphorylation.Clin Cancer Res, 2006, 12:2538-2544.
6. Massarelli E, Varella-Garcia M, Tang X, et al. KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer.Clin Cancer Res, 2007, 13:2890-2896.
7. Mao C, Qiu LX, Liao RY, et al. KRAS mutations and resistance to EGFR-TKIs treatment in patients with non-small cell lung cancer:a meta-analysis of 22 studies. Lung Cancer, 2010, 69:272-278.
8. Marks JL, Broderock S, Zhou Q, et al.Prognostic and therapeutic implications of EGFR and KRAS mutations in respected lung adenocarcinoma.J Thorac Oncol, 2008, 3:111-116.
9. Wu CC, Hsu HY, Liu HP, et al.Reversed mutation rates of KRAS and EGFR genes in adenocarcinoma of the lung in Taiwan and their implications.Cancer, 2008, 113:3199-3208.
10. 张海萍, 付莉, 陈培琼, 等.特异引物双扩增即时PCR与传统测序法检测肠癌、肺癌患者K-ras基因突变的比较.中华病理学杂志, 2010, 39:757-761.
11. 罗炜, 王慧, 徐韫健, 等.非小细胞肺癌患者KRAS基因突变情况分析.广东医学, 2014, 35:2025-2028.
12. 张卉, 杨新杰, 秦娜, 等.肺腺癌EGFR与KRAS基因突变状态分析.中国肺癌杂志, 2015, 18:686-690.
13. 张卉, 杨新杰, 秦娜, 等.肺鳞癌EGFR与KRAS基因突变状态分析.中国肺癌杂志, 2015, 18:621-625.
14. 衣素琴, 庄园, 朱卫东, 等.非小细胞肺癌中KRAS基因突变分析.中华临床医师杂志(电子版), 2013, 7:9111-9115.
15. 许春伟, 张立英, 吴永芳, 等.非小细胞肺癌患者外周血与组织中K-ras基因突变的研究.贵州医药, 2015, 39:1-3.
16. Wu S, Zhu Z, He J, et al.A novel mutant-enriched liquidchip technology for the qualitative detection of somatic mutations in KRAS gene from both serum and tissue samples.Clin Chem Lab Med, 2010, 48:1103-1106.

Chinese Journal of Respiratory and Critical Care Medicine

Detection of K-ras Gene Mutations in Peripheral Blood Free DNA in Patients with Non-Small Cell Lung Cancer

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