Circulating mRNA Expression of Astrocyte-Elevated Gene-1 Associated with Treatment Response and Survival in Non-Small Cell Lung Cancer Patients Treated with Pemetrexed

Abstract

Background: Astrocyte-elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis in non-small cell lung cancer (NSCLC). In this prospective study, we assessed the values of plasma AEG-1 mRNA expression by liquid biopsy associated with tumour response and survival in NSCLC patients treated with pemetrexed. Methods: Patients diagnosed with advanced NSCLC were enrolled to be treated with pemetrexed combined with platinum as first-line chemotherapy. All patients underwent blood sampling before any cancer treatment (C0) and at first response evaluation after two cycles (C2) of treatments. Response to chemotherapy and survival were assessed. Plasma mRNA was extracted from peripheral blood mononuclear cell (PBMC) and quantification of RNA was performed by real-time PCR. Results: A total of 50 patients with advanced NSCLC were included and 13 of 50 patients combined with bevacizumab. In patient groups of stable disease (SD) (n = 13) and progressive disease (PD) (n = 10), the plasma mRNA of AEG-1, thymidylate synthase (TS), and CK19 were elevated significantly at C2 compared to patients in treatment response group (PR, n = 27) (PR vs. SD or PD, AEG-1: 1.22 ± 0.80 vs. 4.51 ± 15.45, p = 0.043). NSCLC patients who had elevated AEG-1 (AEG-1 ≥ 2) after two cycles of chemotherapy had shorter PFS and OS (high AEG-1 vs. low AEG-1, median, PFS: 5.5 vs. 11.9 months, p = 0.021; OS: 25.9 vs. 40.8 months, p = 0.019, respectively). In a Cox regression analysis, increased plasma mRNA expression of AEG-1indicated poor prognosis in survival. Conclusions: Circulating mRNA concentration of AEG-1 could be a predictive and prognostic biomarker in NSCLC patients treated with pemetrexed. Increased expression of AEG-1 contributed to the chemoresistance and caused lung cancer progression.