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. 2017 May 11;18(5):1035.
doi: 10.3390/ijms18051035.

Circulating Cell-Free DNA and Circulating Tumor Cells as Prognostic and Predictive Biomarkers in Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Chemotherapy

Simona Coco  1 , Angela Alama  2 , Irene Vanni  3 , Vincenzo Fontana  4 , Carlo Genova  5   6 , Maria Giovanna Dal Bello  7 , Anna Truini  8   9 , Erika Rijavec  10 , Federica Biello  11 , Claudio Sini  12 , Giovanni Burrafato  13 , Claudia Maggioni  14 , Giulia Barletta  15 , Francesco Grossi  16
Affiliations

Circulating Cell-Free DNA and Circulating Tumor Cells as Prognostic and Predictive Biomarkers in Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Chemotherapy

Simona Coco et al. Int J Mol Sci. .

Abstract

Cell-free DNA (cfDNA) and circulating tumor cells (CTCs) are promising prognostic and predictive biomarkers in non-small cell lung cancer (NSCLC). In this study, we examined the prognostic role of cfDNA and CTCs, in separate and joint analyses, in NSCLC patients receiving first line chemotherapy. Seventy-three patients with advanced NSCLC were enrolled in this study. CfDNA and CTC were analyzed at baseline and after two cycles of chemotherapy. Plasma cfDNA quantification was performed by quantitative PCR (qPCR) whereas CTCs were isolated by the ScreenCell Cyto (ScreenCell, Paris, France) device and enumerated according to malignant features. Patients with baseline cfDNA higher than the median value (96.3 hTERT copy number) had a significantly worse overall survival (OS) and double the risk of death (hazard ratio (HR): 2.14; 95% confidence limits (CL) = 1.24-3.68; p-value = 0.006). Conversely, an inverse relationship between CTC median baseline number (6 CTC/3 mL of blood) and OS was observed. In addition, we found that in patients reporting stable disease (SD), the baseline cfDNA and CTCs were able to discriminate patients at high risk of poor survival. cfDNA demonstrated a more reliable biomarker than CTCs in the overall population. In the subgroup of SD patients, both biomarkers identified patients at high risk of poor prognosis who might deserve additional/alternative therapeutic interventions.

Keywords: biomarkers; chemotherapy; circulating free DNA; circulating tumor cells; liquid biopsy; non-small cell lung cancer (NSCLC).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overall survival according to circulating biomarkers at baseline by Kaplan–Meier analysis. Non-small cell lung cancer (NSCLC) patients were divided into two groups according to median baseline values. (A) Cell-free DNA (cfDNA): 96.3 human Telomerase Reverse Transcriptase (hTERT) copy number (p-value = 0.019); (B) Circulating tumor cells (CTCs): 6 CTCs/3 mL of blood (p-value = 0.402).
Figure 2
Figure 2
Curves of cumulative death and relapse rates according to cfDNA and CTCs by Cox regression modeling. Death (A) and relapse (B) rates estimated by cfDNA hTERT copy number. Death (C) and relapse (D) rates estimated by CTC number.
Figure 3
Figure 3
Morphological analysis of NSCLC cells entrapped on a ScreenCell Cyto device filter. The black arrows indicate non-hematologic circulating cells with malignant features. (A) Adenocarcinoma (H&E staining, magnification 40×); (B) Squamous cell carcinoma (H&E staining, magnification 40×); (C) Microemboli (H&E staining, magnification 40×). Micropores dimension: 7.5 ± 0.36 μm.
See this image and copyright information in PMC

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