Plasma dynamic monitoring of soluble c-Met level for EGFR-TKI treatment in advanced non-small cell lung cancer
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Hong-Fei Gao1,2, Jin-Ji Yang2, Zhi-Hong Chen2, Xu-Chao Zhang2, Hong-Hong Yan2, Wei-Bang Guo2, Qing Zhou2, Lou-Ying Gou2, Zhong-Yi Dong2 and Yi-Long Wu2
1 Guangdong Cardiovascular Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China
2 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China
Yi-Long Wu, email:
Keywords: soluble c-Met, EGFR-TKI, NSCLC
Received: December 07, 2015 Accepted: April 16, 2016 Published: May 18, 2016
Background: The activation of c-Met has been associated with both primary and acquired resistance to EGFR-TKI therapy in NSCLC patients. Thus, c-Met status during EGFR-TKI therapy should receive much attention.
Results: Forty-nine patients were selected as training cohort and 52 cases as validation cohort. With disease progression, IHC results showed that 37 (75.5%) of the patients were tissue c-Met-negative, and 12 (24.5%) were tissue c-Met-positive. There was a statistically significant difference in the dynamic change in soluble c-Met between the tissue c-Met-negative and c-Met-positive groups (P = 0.002). Patients with a baseline soluble c-Met level >766 ng/ml showed inferior median progression-free survival (PFS; 10.2 vs. 14.0 months; P = 0.003) after EGFR-TKI treatment. Multivariate Cox proportional hazards model analyses demonstrated that the soluble c-Met level was an independent prognostic factor for PFS after EGFR-TKI treatment (P = 0.009; hazard ratio: 3.583; 95% confidence interval: 1.379-9.312). In the validation cohort, patients with soluble c-Met levels >766 ng/ml were also determined to have significant short median PFS after EGFR-TKI treatment (6.8 vs. 14.5 months, P < 0.001).
Patients and Methods: We retrospectively investigated the dynamic change in the soluble c-Met level in plasma and its relationship with clinical outcomes of EGFR-TKI therapy in advanced NSCLC. Immunohistochemistry (IHC) was used to assess the expression of c-Met in the resistant tissue. Plasma c-Met levels were assayed in duplicate using a human soluble c-Met quantitative enzyme-linked immunosorbent assay (ELISA) kit.
Conclusions: Quantitatively determining the soluble c-Met level in plasma by ELISA might provide a non-invasive and sensitive method to predict EGFR-TKI prognosis.
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