CD133+CD54+CD44+ circulating tumor cells as a biomarker of treatment selection and liver metastasis in patients with colorectal cancer

Oncotarget. 2016 Nov 22;7(47):77389-77403. doi: 10.18632/oncotarget.12675.

Abstract

Introduction: Liver is the most common site of distant metastasis in colorectal cancer (CRC). Early diagnosis and appropriate treatment selection decides overall prognosis of patients. However, current diagnostic measures were basically imaging but not functional. Circulating tumor cells (CTCs) known as hold the key to understand the biology of metastatic mechanism provide a novel and auxiliary diagnostic strategy for CRC with liver metastasis (CRC-LM).

Results: The expression of CD133+ and CD133+CD54+CD44+ cellular subpopulations were higher in the peripheral blood of CRC-LM patients when compared with those without metastasis (P<0.001). Multivariate analysis proved the association between the expression of CD133+CD44+CD54+ cellular subpopulation and the existence of CRC-LM (P<0.001). The combination of abdominal CT/MRI, CEA and the CD133+CD44+CD54+ cellular subpopulation showed increased detection and discrimination rate for liver metastasis, with a sensitivity of 88.2% and a specificity of 92.4%. Meanwhile, it also show accurate predictive value for liver metastasis (OR=2.898, 95% C.I.1.374-6.110).

Materials and methods: Flow cytometry and multivariate analysis was performed to detect the expression of cancer initiating cells the correlation between cellular subpopulations and liver metastasis in patients with CRC. The receiver operating characteristic curves combined with the area under the curve were generated to compare the predictive ability of the cellular subpopulation for liver metastasis with current CT and MRI images.

Conclusions: The identification, expression and application of CTC subpopulations will provide an ideal cellular predictive marker for CRC liver metastasis and a potential marker for further investigation.

Keywords: CD133+CD54+CD44+ cellular subpopulation; circulating tumor cells; colorectal cancer; liver metastasis; predictive biomarker.

MeSH terms

  • AC133 Antigen / metabolism*
  • Aged
  • Area Under Curve
  • Biomarkers
  • Colorectal Neoplasms / diagnostic imaging
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / therapy
  • Female
  • Flow Cytometry
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / therapy
  • Male
  • Middle Aged
  • Multimodal Imaging / methods
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • ROC Curve

Substances

  • AC133 Antigen
  • Biomarkers
  • CD44 protein, human
  • Hyaluronan Receptors
  • Intercellular Adhesion Molecule-1