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The role of circulating tumor cells and K-ras mutations in patients with locally advanced rectal cancer: a prospective study

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Abstract

Rectal cancer is a common malignancy with a relatively poor prognosis. We assessed the possible prognostic and predictive role(s) of circulating tumor cells (CTCs) and K-ras mutations in locally advanced rectal carcinoma (LARC) patients. CTCs number and K-ras mutation status were assessed in the Peripheral blood and tumor tissue samples of 60 patients with LARC compared to control group (normal rectal mucosa). Data were correlated to relevant clinico-pathological features, response to treatment, disease free (DFS) and overall survival (OS) rates. K-ras mutations were present in 24/60 (40%) patients. Baseline CTCs (< 5 cells/7 ml blood) were detected in 23/60 (38.3%) patients, and 37 (61.7%) had baseline CTCs (≥ 5 cells/7 ml) blood (P = 0.071). Serial sampling showed a decrease in CTCs levels in 40 (66.7%) patients and increase in 20 (33.3%) patients (P = 0.01). Patients with K-ras mutations had a significantly poor response to treatment, with reduced DFS and OS rates (P = 0.001, 0.004, and 0.001; respectively). Similarly, decreased CTCs levels during treatment associated significantly with better pathological responses (P = 0.003). Multivariate analysis demonstrated that K-ras mutation and baseline CTCs are independent prognostic factors for DFS (P = 0.014 and 0.045; respectively) and OS (P = 0.002 and 0.045; respectively). The presence of mutant K-ras and baseline CTCs ≥ 5 cells associated significantly with poor pathological response, shorter DFS and OS rates compared to those with either K-ras mutation or CTCs ≥ 5 cells only (P = 0.014, 0.005 and 0.001, respectively). K-ras mutations, baseline and serial CTCs changes represent good prognostic and predictive factors for LARC patients.

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Funding

This study is supported by National Cancer Institute, Cairo University.

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Authors and Affiliations

  1. Pathology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt

    Abeer A. Bahnassy & Asmaa Salama

  2. Department of Radiation Oncology, National Cancer Institute, Cairo University, Cairo, 11976, Egypt

    Yasser A. Abdel-Azim & Somaya Ezzat

  3. Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt

    Mona S. Abdellateif

  4. Molecular Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt

    Abdel-Rahman N. Zekri

  5. Biochemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, MISR University for Science and Technology, 6th October, 12945, Egypt

    Marwa Mohanad

  6. Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, 11976, Egypt

    Hussein Khaled

Authors
  1. Abeer A. Bahnassy
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  2. Yasser A. Abdel-Azim
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  3. Somaya Ezzat
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  4. Mona S. Abdellateif
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  5. Abdel-Rahman N. Zekri
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  7. Asmaa Salama
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  8. Hussein Khaled
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Correspondence to Abeer A. Bahnassy.

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All authors approve the submission and declare no competence of interest.

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The study protocol was approved by the ethical committee of the institutional review board of the NCI, Cairo University, which is in accordance to the 2017 declaration of Helsinki.

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Bahnassy, A.A., Abdel-Azim, Y.A., Ezzat, S. et al. The role of circulating tumor cells and K-ras mutations in patients with locally advanced rectal cancer: a prospective study. Mol Biol Rep 47, 9645–9657 (2020). https://doi.org/10.1007/s11033-020-05973-8

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  • DOI: https://doi.org/10.1007/s11033-020-05973-8

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