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Prognostic significance of CEACAM5mRNA-positive circulating tumor cells in patients with metastatic colorectal cancer

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Abstract

Purpose

Τo evaluate the clinical relevance of CEACAM5mRNA-positive circulating tumor cells (CTCs) in patients with metastatic colorectal cancer (mCRC).

Methods

Peripheral blood was obtained from 436 patients with mCRC before the initiation of systemic therapy. A second sample was obtained on treatment assessment from 296 (67.9%) patients. The detection of CEACAM5mRNA-positive CTCs was performed using a real-time PCR assay.

Results

The patients’ median age was 67 years and PS (EGOG 0–1) 92%; KRAS exon 2 and BRAFV600E mutated primary tumors were identified in 31.9% and 6.4% of the tested patients, respectively, whereas metastasectomy was performed in 17.7% of the patients. Circulating CEACAM5mRNA-positive CTCs were detected in 125 (28.7%) and 85 (28.7%) patients at baseline and on treatment assessment, respectively. The detection of CEACAM5mRNA-positive cells was revealed, in multivariate analysis, as an independent prognostic factor associated with decreased PFS (HR 1.6; 95% CI 1.1–2.5; p = 0.026) and OS (HR 2.2; 95% CI 1.3–3.2; p < 0.001). The detection of CEACAM5mRNA-positive CTCs in patients with KRAS and BRAFV600E mutations was correlated with shorter PFS (p = 0.041 and p = 0.022, respectively). Moreover, OS was significantly shorter in patients with CEACAM5+/KRAS mutations compared to those with CEACAM5+/KRAS wt tumors (p = 0.023).

Conclusions

Detection of peripheral blood CEACAM5mRNA-positive CTCs is an adverse prognostic factor correlated with poor clinical outcome in patients with mCRC, especially in patients with KRAS and BRAF mutated tumors.

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Acknowledgements

This work was partly supported by the Cretan Association for Biomedical Research (CABR), the Hellenic Society of Medical Oncology (HeSMO) and the SYNERGASIA 2009 PROGRAMME (co-funded by the European Regional Development Fund and the General Secretariat of Research and Technology in Greece), Project code: Onco-Seed diagnostics.

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Authors and Affiliations

  1. Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Stavrakia and Voutes, 71100, Heraklion, Crete, Greece

    Ippokratis Messaritakis, Maria Sfakianaki, Chara Papadaki, Asimina Koulouridi, Dora Hatzidaki, Nefeli Georgoulia, Athanasios Kotsakis, John Souglakos & Vassilis Georgoulias

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

    Nikolaos Vardakis, Filippos Koinis, Athanasios Kotsakis & John Souglakos

  3. Medical School, University of Athens, Athens, Greece

    Athina Kladi

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  1. Ippokratis Messaritakis
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Correspondence to Vassilis Georgoulias.

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280_2018_3666_MOESM1_ESM.tif

Supplementary Figure 1 Kaplan Meier curves for progression-free survival (A) and overall survival (B) according to CEACAM5mRNA positivity and KRAS status at baseline and for progression-free survival (C) and overall survival (D) according to CEACAM5mRNA positivity and BRAF status at baseline (TIF 189 KB)

Supplementary material 2 (DOC 31 KB)

Supplementary material 3 (DOC 33 KB)

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Messaritakis, I., Sfakianaki, M., Papadaki, C. et al. Prognostic significance of CEACAM5mRNA-positive circulating tumor cells in patients with metastatic colorectal cancer. Cancer Chemother Pharmacol 82, 767–775 (2018). https://doi.org/10.1007/s00280-018-3666-9

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  • DOI: https://doi.org/10.1007/s00280-018-3666-9

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