Ying Fan1,2, Rui Sun3,4, Zhizhong Wang3,4, Yuying Zhang2, Xiao Xiao2, Yizhe Liu2, Beibei Xin2, Hui Xiong2, Daru Lu5,6, Jie Ma7,8. 1. State Key Laboratory of Genetic Engineering and MOE Engineering Research Center of Gene Technology, School of Life Sciences, Fudan University, Shanghai, 200438, Shanghai, China. 2. Shanghai Yuanqi Biomedical Technology Co., Ltd., Shanghai, 201403, China. 3. Department of Molecular Pathology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450003, China. 4. Henan Key Laboratory of Molecular Pathology, Zhengzhou, 450003, China. 5. State Key Laboratory of Genetic Engineering and MOE Engineering Research Center of Gene Technology, School of Life Sciences, Fudan University, Shanghai, 200438, Shanghai, China. drlu@fudan.edu.cn. 6. NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning, Science and Technology Research Institute, Chongqing, 400014, China. drlu@fudan.edu.cn. 7. Department of Molecular Pathology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450003, China. majie_henanch@163.com. 8. Henan Key Laboratory of Molecular Pathology, Zhengzhou, 450003, China. majie_henanch@163.com.
Abstract
PURPOSE: Mesenchymal-epithelial transition (MET) amplification is one of the mechanisms accounting for the resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in lung cancer patients, as well as the poor prognosis. Fluorescence in situ hybridization (FISH) is the most widely used method for MET amplification detection. However, it is inapplicable when tissue samples were unavailable. Herein, we assessed the value of droplet digital PCR (ddPCR) in MET copy number gain (CNG) detection in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKIs. MATERIALS AND METHODS: A total of 103 cancer tissues and the paired peripheral blood samples from NSCLC patients were collected for MET CNG detection using ddPCR. In parallel, MET amplification in tissue samples was verified by FISH. Also, the relationships between MET CNG and EGFR T790M, as well as the EGFR-TKI resistance were also evaluated using Chi-square or Fisher's exact tests. RESULT: The concordance rate of ddPCR and FISH in detecting MET CNG in tissue samples was 100% (102/102), and it was 94.17% (97/103) for ddPCR method in detecting the MET CNG among peripheral blood and tissue samples. No statistical difference was observed between MET amplification and EGFR T790M (p = 0.65), while MET amplification rate was significantly increased in patients with resistance to third generations of EGFR-TKIs as compared with patients with resistance to first/second EGFR-TKIs (p < 0.05). CONCLUSIONS: ddPCR is an alternative method to detect MET CNG in both tissues and peripheral blood samples, which is of worthy in clinical promotion.
PURPOSE: Mesenchymal-epithelial transition (MET) amplification is one of the mechanisms accounting for the resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in lung cancer patients, as well as the poor prognosis. Fluorescence in situ hybridization (FISH) is the most widely used method for MET amplification detection. However, it is inapplicable when tissue samples were unavailable. Herein, we assessed the value of droplet digital PCR (ddPCR) in MET copy number gain (CNG) detection in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKIs. MATERIALS AND METHODS: A total of 103 cancer tissues and the paired peripheral blood samples from NSCLC patients were collected for MET CNG detection using ddPCR. In parallel, MET amplification in tissue samples was verified by FISH. Also, the relationships between MET CNG and EGFR T790M, as well as the EGFR-TKI resistance were also evaluated using Chi-square or Fisher's exact tests. RESULT: The concordance rate of ddPCR and FISH in detecting MET CNG in tissue samples was 100% (102/102), and it was 94.17% (97/103) for ddPCR method in detecting the MET CNG among peripheral blood and tissue samples. No statistical difference was observed between MET amplification and EGFR T790M (p = 0.65), while MET amplification rate was significantly increased in patients with resistance to third generations of EGFR-TKIs as compared with patients with resistance to first/second EGFR-TKIs (p < 0.05). CONCLUSIONS: ddPCR is an alternative method to detect MET CNG in both tissues and peripheral blood samples, which is of worthy in clinical promotion.
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