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

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. Electronic supplementary material The online version of this article (10.1007/s10120-018-0894-y) contains supplementary material, which is available to authorized users.

Serum Insulin-Like Growth Factor Binding Protein 7 as a Potential Biomarker in the Diagnosis and Prognosis of Esophagogastric Junction Adenocarcinoma

“… 29 A recent study on serum autoantibody panels to detect EJA aroused our interest to identify noninvasive techniques to detect IGFBP7 in EJA patient serum. 16 When accounting for the early detection of IGFBP7 in EJA, through ROC curve analysis, we found an AUC of 0.749 (95% CI, 0.644 to 0.854), which led to a sensitivity of 54.3% (95% CI, 36.9% to 70.8%) and specificity of 90.9% (95% CI, 82.4% to 95.7%). Although there was no statistical correlation between late-stage and early-stage EJA (p=0.187) ( Table 4 ), IGFBP7 might be used as a potential biomarker for the early detection of EJA.…”

“… 3 In accordance with our previous study, American Joint Committee on Cancer stage I+II was defined as early-stage EJA. 16 …”

The Diagnostic Value of Serum IGFBP7 in Patients with Esophageal Squamous Cell Carcinoma

“…What's more, the prognostic value could be included in the further study as some researches showed that there is a probable correlation between IGFBP7 and cancer prognosis 36,42. In addition, as a panel of serum biomarkers could enhance diagnostic efficiency 14,32,43, we could combine serum IGFBP7 with other serum markers or even other types of test to explore the improvement compared to the alone marker.…”

Autoantibodies: Potential clinical applications in early detection of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma

“…Likewise, a similar phenomenon has been observed in the studies on autoantibodies for the diagnosis of EGJA. As can be seen from Table 3, a total of 13 autoantibodies were investigated in two studies[41,42], all of which were initially assessed in ESCC by Xu et al[43] and Zhou et al[44]. As anticipated, the presence of TA autoantibodies indicates early diagnostic potential for EGJA.…”

“…This optimized combination is somewhat different from an optimized panel identified for ESCC (p53, IMP1, P16, cyclin B1, P62 and c-Myc) studied by the same research team. Subsequently, Xu et al[42] showed that autoantibodies against a combination of p53, NY-ESO-1, MMP-7, Hsp70, PRDX6 and Bmi-1, which is the same as the panel used for evaluation of ESCC, could be potentially used for early diagnosis of EGJA. When comparing stage I and II patients to normal controls, the authors showed sensitivities and specificities of 50.0% and 90.5% and 56.0% and 90.0%, respectively, in the training and validation cohorts.…”