title: Combined detection of serum Dickkopf-1 and its autoantibodies to diagnose esophageal squamous cell carcinoma.
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.
authors.affiliation: Department of Clinical Laboratory, The Cancer Hospital of Shantou University Medical College, Shantou, China.|The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Peng
authors.affiliation: Department of Clinical Laboratory, The Cancer Hospital of Shantou University Medical College, Shantou, China.|The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China.|Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Xu
authors.affiliation: Department of Radiation Oncology, The Cancer Hospital of Shantou University Medical College, Shantou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Radiation Oncology, The Cancer Hospital of Shantou University Medical College, Shantou, China.
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China.
authors.forename: Hua-Zhen
authors.initials: HZ
authors.lastname: Tan
authors.affiliation: Department of Oncological Research Lab, The Cancer Hospital of Shantou University Medical College, Shantou, China.
authors.forename: Chao-Qun
authors.initials: CQ
authors.lastname: Hong
authors.affiliation: Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Li
authors.affiliation: The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China.|Institute of Oncologic Pathology, Shantou University Medical College, Shantou, China.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Xu
authors.affiliation: The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China.|Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China.
authors.forename: En-Min
authors.initials: EM
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000175:diagnosis*; D055088:Early Detection of Cancer; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000097:blood* / Q000175:diagnosis*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012372:ROC Curve; D047368:Tumor Burden
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins
keywords: DKK-1 autoantibody; Dickkopf-1 (DKK-1); early diagnosis; esophageal squamous cell carcinoma (ESCC)