Abstract

BackgroundLung cancer is the leading cause of cancer-related mortality worldwide. At diagnosis, 70% of patients present advanced disease being chemotherapy the standard of care. Although, specific tumour biomarkers that allow a better treatment selection and monitoring is absent at the moment. Enumeration and characterization of circulating tumor cells (CTCs) have the potential to perform as a prognostic biomarker for a precision medicine approach to lung cancer care. The present study was conducted to validate the characterization CTCs from patients with advanced Non-small cell lung cancer (NSCLC) as a valuable tool for anticipating the disease evolution and the therapy response. Methods78 patients with advanced NSCLC were enrolled in the study at HGUV and CHUS. EpCAM positive CTCs from these patients were isolated and analysed using both CellSearch technology and a qRT-PCR based approach at different times: at baseline and before the 2nd and 5th cycle treatment. A panel of genes with a relevant role for NSCLC aggressiveness and the resistance to platinum-based treatments were analysed. ResultsFrom all patients included in the study 46% were positive for CTCs using CellSearch system at baseline, showing only 12% of patients ≥5 CTCs. Additionally, patients with ≥5 CTCs showed poor PFS (4.66 vs 7.12 months, p=0.040) and OS (3,9 vs 13.43 months, p<0.001) rates compared with those patients with <5CTCs. In addition, patients with high CTCs levels during treatment also had a more aggressive disease evolution in terms of PFS and OS (p=0.007 and p=0.001, respectively). From the analyzed gene panel, patients with lower CHOKα expression at baseline had increased PFS (7.03 vs. 3.9 months, p=0.009) and OS (11.4 vs. 4.07 months, p=0.001). Furthermore, we found low CHOK α levels as a powerful marker to discriminate patients with a good response to chemotherapy from those that progressed during treatment administration (14.35 vs 5.07 months, respectively, p=0.011). ConclusionsWe demonstrated that quantification and gene expression characterization of CTCs represents an adequate strategy to identify prognostic biomarkers in NSCLC patients Supported by RTC-2014-1532-1 from MINECO and CB16/12/00350-CB16/12/00328 from CIBERONC. Legal entity responsible for the studyFIHGUV. FundingSupported from RTC-2014-1532-1 (Spanish Ministry of Economy, Industry and Competitiveness) and CB16/12/00350 and CB16/12/00328 from CIBERONC. DisclosureAll authors have declared no conflicts of interest.

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