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Prognostic value of chemotherapy-resistant CK19mRNA-positive circulating tumor cells in patients with advanced/metastatic non-small cell lung cancer

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Abstract

Background

The detection of circulating tumor cells (CTCs) is of prognostic significance in several tumor types. The present study evaluated the detection and the clinical relevance of CK19mRNA(+) CTCs in patients with advanced/metastatic non-small cell lung cancer before and after front-line chemotherapy.

Patients and methods

Peripheral blood was obtained from 642 patients with treatment-naïve unresectable stage IIIB and IV non-small cell lung cancer and from 455 patients after the completion of 1st line chemotherapy. RNA was extracted from peripheral blood mononuclear cells and the detection of CK19mRNA-positive cells was performed using a quantitative PCR assay.

Results

Based on the detection limit of the assay, 167 (26.0%) patients had detectable CK19mRNA(+) CTCs at baseline. The detection of CK19mRNA(+) CTCs before treatment was not associated with the clinical outcome, but their detection at the end of chemotherapy was associated with significantly decreased PFS and OS [PFS: 2.6 vs 3.8 months (p = 0.008); OS: 5.7 vs 10.0 months (p = 0.006) for CK19mRNA(+) vs CK19mRNA(−) patients, respectively]. Multivariate analysis revealed that the detection of CK19mRNA(+) CTCs both before and after chemotherapy emerged as an independent factor associated with reduced PFS (HR: 1.778; p < 0.001) and OS (HR: 1.608; p = 0.001).

Conclusion

The detection of peripheral blood CK19mRNA(+) CTCs before and after the completion of front-line chemotherapy is an adverse prognostic factor associated with poor clinical outcome in patients with stage IIIB/IV non-small cell lung cancer.

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Acknowledgements

We acknowledge the assistance of the scientific secretary Vasso Athanasaki in the preparation of this manuscript.

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Author notes

  1. G. Milaki and I. Messaritakis contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, 71110, Heraklion, Crete, Greece

    G. Milaki, I. Messaritakis, F. Koinis, A. Kotsakis, S. Apostolaki, E. K. Dermitzaki, M. Perraki, D. Hatzidaki & V. Georgoulias

  2. Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Crete, Greece

    A. Kotsakis

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  1. G. Milaki
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Correspondence to V. Georgoulias.

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Funding

This work was partly supported by research grants from the Cretan Association for Biomedical Research (CABR) and the Hellenic Society of Medical Oncology (HeSMO).

Conflict of interest

Milaki G, Messaritakis I, Koinis F, Kotsakis A, Apostolaki S, Dermitzaki EK, Perraki M, Hatzidaki D, and Georgoulias V declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Milaki, G., Messaritakis, I., Koinis, F. et al. Prognostic value of chemotherapy-resistant CK19mRNA-positive circulating tumor cells in patients with advanced/metastatic non-small cell lung cancer. Cancer Chemother Pharmacol 80, 101–108 (2017). https://doi.org/10.1007/s00280-017-3339-0

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