DCLK1 is detectable in plasma of patients with Barrett's esophagus and esophageal adenocarcinoma

Dig Dis Sci. 2015 Feb;60(2):509-13. doi: 10.1007/s10620-014-3347-4. Epub 2014 Oct 5.

Abstract

Background: Doublecortin-like kinase 1 (DCLK1), a putative tumor stem cell marker has been shown to be highly expressed in the stromal and epithelial compartments in colon and pancreatic cancer as well as Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC).

Aim: To prospectively investigate whether the immunohistochemical expression of DCLK1 was associated with detectable DCLK1 plasma expression in patients with existing BE and EAC.

Methods: Immunohistochemistry was performed on paraffin-embedded sections using DCLK1 antibody and scored based on staining intensity and tissue involvement. Purified human plasma samples were subjected to Western blot and ELISA analysis.

Results: Forty (40) patients were enrolled: 10 controls (normal endoscopy) and 30 with BE/EAC (13 nondysplastic BE [NDBE], 9 dysplastic BE [DBE] and 8 EAC). Mean epithelial DCLK1 staining was as follows: controls = 0.11, NDBE = 3.83, DBE = 6.0, EAC = 7.17. Mean stromal DCLK1 staining was as follows: NDBE = 5.83, DBE = 5.375, EAC = 10.83. DCLK1 was detected by plasma Western blot in 1 control and in all patients with BE/EAC p < 0.0005. Plasma DCLK1 was elevated by ELISA in EAC compared to other groups, p < 0.05.

Conclusions: Increased expression of DCLK1 was observed in the epithelium, stroma and plasma of patients with BE/EAC. Furthermore, the presence of detectable DCLK1 in plasma of BE/EAC patients may provide a less invasive, detection tool in those patients as well as represent a novel molecular marker distinguishing between normal esophageal mucosa and BE or EAC.

Publication types

  • Observational Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / pathology
  • Barrett Esophagus / blood
  • Barrett Esophagus / enzymology*
  • Barrett Esophagus / pathology
  • Biomarkers, Tumor / blood*
  • Blotting, Western
  • Case-Control Studies
  • Doublecortin-Like Kinases
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / enzymology
  • Esophageal Neoplasms / blood
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / pathology
  • Esophagoscopy
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / blood*
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Protein Serine-Threonine Kinases / blood*
  • Stromal Cells / enzymology
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • DCLK1 protein, human
  • Doublecortin-Like Kinases
  • Protein Serine-Threonine Kinases

Supplementary concepts

  • Adenocarcinoma Of Esophagus