Combined detection of serum autoantibodies as diagnostic biomarkers in esophagogastric junction adenocarcinoma

Gastric Cancer. 2019 May;22(3):546-557. doi: 10.1007/s10120-018-0894-y. Epub 2018 Nov 13.

Abstract

Background: We previously found that autoantibodies against a panel of six tumor-associated antigens (p53, NY-ESO-1, MMP-7, Hsp70, PRDX6 and Bmi-1) may aid in early detection of esophageal squamous cell carcinoma. Here we aimed to evaluate the diagnostic value of this autoantibody panel in esophagogastric junction adenocarcinoma (EJA) patients.

Methods: Serum autoantibody levels were measured by enzyme-linked immunosorbent assay in a training cohort and a validation cohort. We used receiver-operating characteristics (ROC) to calculate diagnostic accuracy.

Results: We recruited 169 normal controls and 122 EJA patients to the training cohort, and 80 normal controls and 70 EJA patients to the validation cohort. Detection of the autoantibody panel demonstrated an area under the curve (AUC) of 0.818, sensitivity 59.0% and specificity 90.5% in training cohort, and AUC 0.815, sensitivity 61.4% and specificity 90.0% in validation cohort in the diagnosis of EJA. Measurement of the autoantibody panel could distinguish early stage EJA patients from normal controls (AUC 0.786 and 0.786, sensitivity 50.0% and 56.0%, and specificity 90.5% and 90.0%, for training and validation cohorts, respectively). Moreover, a restricted panel consisting of autoantibodies against p53, NY-ESO-1 and Bmi-1 exhibited similar diagnostic performance for EJA (AUC 0.814 and 0.823, sensitivity 53.5% and 60.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively) and early stage EJA (AUC 0.744 and 0.773, sensitivity 55.6% and 52.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively).

Conclusions: Autoantibodies against an optimized TAA panel as serum biomarkers appear to help identify the present of early stage EJA.

Keywords: Autoantibody; Diagnosis; Esophagogastric junction adenocarcinoma; Tumor-associated antigen.

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / immunology
  • Adenocarcinoma / secondary*
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Biomarkers, Tumor / immunology*
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / secondary*
  • Carcinoma, Squamous Cell / surgery
  • Case-Control Studies
  • Early Detection of Cancer
  • Esophageal Neoplasms / blood
  • Esophageal Neoplasms / immunology
  • Esophageal Neoplasms / pathology*
  • Esophageal Neoplasms / surgery
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • ROC Curve
  • Retrospective Studies

Substances

  • Autoantibodies
  • Biomarkers, Tumor