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Tumor Biology

, Volume 36, Issue 6, pp 4801–4810 | Cite as

Upregulation of circulating cancer stem cell marker, DCLK1 but not Lgr5, in chemoradiotherapy-treated colorectal cancer patients

  • Alireza Mirzaei
  • Gholamreza Tavoosidana
  • Mohammad Hossein Modarressi
  • Afshin Abdi Rad
  • Mohammad Sadegh Fazeli
  • Reza Shirkoohi
  • Masoumeh Tavakoli-Yaraki
  • Zahra Madjd
Research Article

Abstract

Cancer stem cell (CSC) markers have attracted considerable attention in tumor diagnostic, prognostic, and therapeutic implications. Detection of cancer stem cells in circulating blood using cancer stem cell markers has received remarkable attention recently. In this study, we aimed to investigate the messenger RNA (mRNA) expression level of Lgr5 and DCLK1 as most proposed colorectal CSC markers in blood circulation also determine the subsequent association to patients’ clinical and pathological findings. Peripheral blood mononuclear cells (PBMCs) of 58 patients with colorectal cancer at stage I–IV with 33 out of 58 patients undergoing preoperative chemoradiotherapy (CRT), as well as 58 healthy controls have been isolated and the extracted RNAs were analyzed using real-time PCR. The mRNA expression pattern of CSC markers of patients and controls was compared using ΔΔCt method. The expression level of Lgr5 was significantly higher in colorectal cancer (CRC) patients comparing to healthy group (4.8-fold change, p < 0.001). Also there was a significant increase in expression level of Lgr5 in patients at stages III and IV comparing to stages I and II (p = 0.031) and higher grades (p = 0.039) of CRC. The expression of DCLK1 was also elevated in patients significantly (2.7-fold change, p < 0.001) and the related expression was increased by increasing disease stage (p = 0.025). Combination of DCLK1 and Lgr5 markers was analyzed by logistic regression and proved to be a slightly better marker compared to each marker alone. Interestingly the DCLK1 expression level was significantly higher in patients undergoing preoperative CRT (p = 0.041); however, no association to neoadjuvant CRT was observed for Lgr5. Considering the over-expression of  DCLK1 and Lgr5 in circulating blood of CRC patients comparing to controls, our results might emphasize on the presence of CSCs in blood of these patients which might be attributed to their clinical and pathological characteristics and may lead to apply in future clinical implications. Moreover, the higher expression level of DCLK1 in patients undergoing CRT can propose it as a more relevant candidate among CSC markers comparing to Lgr5 for CRC patients.

Keywords

Colorectal cancer Cancer stem cell Chemoradiotherapy DCLK1 Lgr5 

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Alireza Mirzaei
    • 1
  • Gholamreza Tavoosidana
    • 1
  • Mohammad Hossein Modarressi
    • 2
  • Afshin Abdi Rad
    • 3
  • Mohammad Sadegh Fazeli
    • 4
  • Reza Shirkoohi
    • 5
  • Masoumeh Tavakoli-Yaraki
    • 6
  • Zahra Madjd
    • 7
    • 8
  1. 1.Department of Molecular Medicine, School of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran
  2. 2.Department of Medical Genetics, School of MedicineTehran University of Medical SciencesTehranIran
  3. 3.Surgical Pathology Department, Cancer InstituteTehran University of Medical SciencesTehranIran
  4. 4.Department of Surgery, Imam Khomeini HospitalTehran University of Medical SciencesTehranIran
  5. 5.Group of Genetics, Cancer Research Center, Cancer InstituteTehran University of Medical SciencesTehranIran
  6. 6.Department of Biochemistry, Faculty of MedicineIran University of Medical SciencesTehranIran
  7. 7.Department of Molecular Medicine, Faculty of Advanced Technologies in MedicineIran University of Medical SciencesTehranIran
  8. 8.Oncopathology Research CenterIran University of Medical SciencesTehranIran

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