Plasma dynamic monitoring of soluble c-Met level for EGFR-TKI treatment in advanced non-small cell lung cancer

Abstract

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 duringEGFR-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 progressionfree 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 EGFRTKI 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.