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DCLK1 Is Detectable in Plasma of Patients with Barrett’s Esophagus and Esophageal Adenocarcinoma

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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.

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Abbreviations

BE:

Barrett’s esophagus

DBE:

BE with dysplasia

TSCs:

Tumor stem cells

DCLK1:

Doublecortin-like kinase 1

EAC:

Esophageal adenocarcinoma

GERD:

Gastroesophageal reflux disease

HGD:

High-grade dysplasia

LGD:

Low-grade dysplasia

NDBE:

Nondysplastic BE

References

  1. Locke GR 3rd, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County. Minnesota Gastroenterol. 1997;112:1448–1456.

    Article  Google Scholar 

  2. Spechler SJ. Clinical practice. Barrett’s Esophagus. N Engl J Med. 2002;346:836–842.

    Article  PubMed  Google Scholar 

  3. Reid BJ, Sanchez CA, Blount PL, Levine DS. Barrett’s esophagus: cell cycle abnormalities in advancing stages of neoplastic progression. Gastroenterology. 1993;105:119–129.

    CAS  PubMed  Google Scholar 

  4. Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005;97:142–146.

    Article  PubMed  Google Scholar 

  5. Quante M, Bhagat G, Abrams JA, et al. Bile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia. Cancer Cell. 2012;21:36–51.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Tu SP, Quante M, Bhagat G, et al. IFN-gamma inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T-cell apoptosis. Cancer Res. 2011;71:4247–4259.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Sureban SM, May R, Lightfoot SA, et al. DCAMKL-1 regulates epithelial-mesenchymal transition in human pancreatic cells through a miR-200a-dependent mechanism. Cancer Res. 2011;71:2328–2338.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Sureban SM, May R, Mondalek FG, et al. Nanoparticle-based delivery of siDCAMKL-1 increases microRNA-144 and inhibits colorectal cancer tumor growth via a Notch-1 dependent mechanism. J Nanobiotechnol. 2011;9:40.

    Article  CAS  Google Scholar 

  9. Sureban SM, May R, Ramalingam S, et al. Selective blockade of DCAMKL-1 results in tumor growth arrest by a Let-7a MicroRNA-dependent mechanism. Gastroenterology. 2009; 137:649–659, 659 e1-2.

  10. Sureban SM, May R, Weygant N, et al. XMD8-92 inhibits pancreatic tumor xenograft growth via a DCLK1-dependent mechanism. Cancer Lett. 2014;351:151–161.

    Article  CAS  PubMed  Google Scholar 

  11. Sureban SM, May R, Qu D, et al. DCLK1 regulates pluripotency and angiogenic factors via microRNA-dependent mechanisms in pancreatic cancer. PLoS ONE. 2013;8:e73940.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Vega KJ, May R, Sureban SM, et al. Identification of the putative intestinal stem cell marker doublecortin and CaM kinase-like-1 in Barrett’s esophagus and esophageal adenocarcinoma. J Gastroenterol Hepatol. 2012;27:773–780.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Regitnig P, Reiner A, Dinges HP, et al. Quality assurance for detection of estrogen and progesterone receptors by immunohistochemistry in Austrian pathology laboratories. Virchows Arch. 2002;441:328–334.

    Article  CAS  PubMed  Google Scholar 

  14. Hur C, Miller M, Kong CY, et al. Trends in esophageal adenocarcinoma incidence and mortality. Cancer. 2013;119:1149–1158.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Wani S, Falk GW, Post J, et al. Risk factors for progression of low-grade dysplasia in patients with Barrett’s esophagus. Gastroenterology. 2011;141:1179–1186.

    Article  PubMed  Google Scholar 

  16. Bhat S, Coleman HG, Yousef F, et al. Risk of malignant progression in Barrett’s oesophagus patients: results from a large population based study. J Natl Cancer Inst. 2011;103:1049–1057.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Rugge M, Zaninotto G, Parente P, et al. Barrett’s esophagus and adenocarcinoma risk: the experience of the North-Eastern Italian registry (EBRA). Ann Surg. 2012;256:788–794.

    Article  PubMed  Google Scholar 

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Acknowledgments

CWH received grant support from VA Merit Award and OCAST-AR101-030.

Conflict of interest

CWH is a co-founder of COARE Biotechnology Inc; other authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Medicine, Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Joshua Whorton, Sripathi M. Sureban, Randal May, Dongfeng Qu, Mohammad Madhoun, Milton Johnson, William M. Tierney, John T. Maple, Kenneth J. Vega & Courtney W. Houchen

  2. Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Stan A. Lightfoot

  3. OU Cancer Institute, Oklahoma City, OK, 73104, USA

    Sripathi M. Sureban & Courtney W. Houchen

  4. Department of Veterans Affairs Medical Center, Oklahoma City, OK, 73104, USA

    Sripathi M. Sureban, Randal May, Stan A. Lightfoot & Courtney W. Houchen

Authors
  1. Joshua Whorton
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  2. Sripathi M. Sureban
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  3. Randal May
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  4. Dongfeng Qu
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  5. Stan A. Lightfoot
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  6. Mohammad Madhoun
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  7. Milton Johnson
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  8. William M. Tierney
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  9. John T. Maple
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  10. Kenneth J. Vega
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  11. Courtney W. Houchen
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Correspondence to Courtney W. Houchen.

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Whorton, J., Sureban, S.M., May, R. et al. DCLK1 Is Detectable in Plasma of Patients with Barrett’s Esophagus and Esophageal Adenocarcinoma. Dig Dis Sci 60, 509–513 (2015). https://doi.org/10.1007/s10620-014-3347-4

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  • DOI: https://doi.org/10.1007/s10620-014-3347-4

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