Combined detection of serum Dickkopf-1 and its autoantibodies to diagnose esophageal squamous cell carcinoma

Cancer Med. 2016 Jul;5(7):1388-96. doi: 10.1002/cam4.702. Epub 2016 Mar 14.

Abstract

Esophageal squamous cell carcinoma (ESCC) can be treated effectively if diagnosed at an early stage. We evaluated whether measurement of Dickkopf-1 (DKK-1) in combination of DKK-1 autoantibodies in serum may benefit early diagnosis of ESCC. Serum DKK-1 and DKK-1 autoantibodies were measured by enzyme-linked immunosorbent assay in a training cohort (185 ESCC samples vs. 97 normal controls) and validated in a validation cohort (104 ESCC samples vs. 53 normal controls). Receiver operating characteristic (ROC) was applied to calculate diagnostic accuracy. Testing of DKK-1 and DKK-1 autoantibodies together could differentiate ESCC from normal controls (area under the ROC curve [AUC] 0.769, 95% confidence interval (CI), 0.715-0.823, 50.3% sensitivity, and 90.7% specificity in the training cohort; AUC 0.752, 95% CI, 0.675-0.829, 50.0% sensitivity, and 84.9% specificity in the validation cohort). Importantly, the diagnostic performance of the combination of DKK-1 and DKK-1 autoantibodies persisted in early ESCC patients (AUC 0.780, 95% CI, 0.699-0.862, 50.0% sensitivity, and 90.7% specificity in the training cohort; AUC 0.745, 95% CI, 0.626-0.865, 53.8% sensitivity, and 84.9% specificity in the validation cohort). Furthermore, the levels of serum DKK-1 or DKK-1 autoantibody after surgical resection were lower, respectively, compared with the corresponding preoperative samples (P < 0.05). Our results suggest that measurement of DKK-1 combined with DKK-1 autoantibodies is a potentially valuable tool for the early detection of ESCC.

Keywords: DKK-1 autoantibody; Dickkopf-1 (DKK-1); early diagnosis; esophageal squamous cell carcinoma (ESCC).

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Biomarkers, Tumor*
  • Carcinoma, Squamous Cell / blood*
  • Carcinoma, Squamous Cell / diagnosis*
  • Early Detection of Cancer
  • Enzyme-Linked Immunosorbent Assay
  • Esophageal Neoplasms / blood*
  • Esophageal Neoplasms / diagnosis*
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood*
  • Intercellular Signaling Peptides and Proteins / immunology
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • ROC Curve
  • Tumor Burden

Substances

  • Autoantibodies
  • Biomarkers, Tumor
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins