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Methylated DAPK and APC promoter DNA detection in peripheral blood is significantly associated with apparent residual tumor and outcome

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Abstract

Background

Death-associated protein kinase (DAPK) and adenomatous polyposis coli gene (APC) have been recently shown to be associated with outcome in patients with esophageal carcinoma, especially adenocarcinoma. We wanted to validate the correlation of these two markers with outcome by detecting methylated DNA sequences in peripheral blood.

Methods

Circulating cell-free DNA extracted from blood plasma of 59 patients with esophageal cancer was analyzed before and after surgical resection by quantitative real-time methylation-specific RT-PCR (TaqMan™) assays.

Results

Thirty-six of 59 patients (61.0%) with esophageal cancer had detectable levels of methylated DAPK or APC promoter DNA and preoperative detection was significantly associated with an unfavorable prognosis as revealed by multivariate Cox proportional hazards regression analysis [Exp(b) = 4.578; P = 0.01]. The combination of both markers significantly increased sensitivity and specificity for discriminating between short (<2.5 years) and long survivors (P = 0.04, ROC curve analysis). Postoperative APC detection was significantly different if residual tumor was apparent (P = 0.03).

Conclusions

Preoperative measurement of methylated DAPK and APC promoter DNA in peripheral blood may contribute to better estimate postoperative survival chances of patients with esophageal carcinoma, especially adenocarcinoma. The postoperative detection of methylated APC in peripheral blood might provide crucial information on apparent residual tumor and might be used as a “molecular” R0-Marker in addition to the pathologic examination.

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Abbreviations

APC:

Adenomatous polyposis coli gene

MGMT:

O 6-Methylguanine-DNA methyltransferase

DAPK:

Death-associated protein kinase

RT-PCR:

Real-time polymerase chain reaction

SCC:

Squamous cell carcinoma

AUC:

Area under the curve

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Authors and Affiliations

  1. Department of Medicine (Cancer Research), West German Cancer Center, University Hospital Essen, 45122, Essen, Germany

    Andreas-Claudius Hoffmann

  2. Department of Visceral and Vascular Surgery, University of Cologne, 50931, Cologne, Germany

    Daniel Vallböhmer, Klaus Prenzel, Ralf Metzger, Michaela Heitmann, Susanne Neiss, Fredericke Ling, Arnulf H. Hölscher & Jan Brabender

  3. Department of Visceral and Transplantation Surgery, University Hospital of Zurich, 8091, Zurich, Switzerland

    Paul M. Schneider

  4. Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA

    Andreas-Claudius Hoffmann

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  1. Andreas-Claudius Hoffmann
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  2. Daniel Vallböhmer
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  3. Klaus Prenzel
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  8. Arnulf H. Hölscher
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  9. Paul M. Schneider
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  10. Jan Brabender
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Correspondence to Andreas-Claudius Hoffmann.

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Hoffmann, AC., Vallböhmer, D., Prenzel, K. et al. Methylated DAPK and APC promoter DNA detection in peripheral blood is significantly associated with apparent residual tumor and outcome. J Cancer Res Clin Oncol 135, 1231–1237 (2009). https://doi.org/10.1007/s00432-009-0564-x

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  • DOI: https://doi.org/10.1007/s00432-009-0564-x

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