Detection of MET amplification by droplet digital PCR in peripheral blood samples of non-small cell lung cancer

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.

Automated summary

This study evaluated the value of ddPCR in detecting MET amplification in non-small cell lung cancer (NSCLC) patients. The results showed a high concordance between ddPCR and FISH in detecting MET amplification, and a good concordance in MET amplification detection in both blood and tissue samples. Moreover, there was no statistical difference between MET amplification and EGFR T790M, but the rate of MET amplification was significantly increased in patients with resistance to third generations of EGFR-TKIs.