Serum autoantibodies in the early detection of esophageal cancer: a systematic review

Abstract

Antibodies against tumor-associated antigens (TAAs) have been found in serum of patients with various types of cancers and may serve as biomarkers for early detection of esophageal cancer as well. This systematic review aims to give an overview about known autoantibodies and their diagnostic value in esophageal cancer. We conducted a systematic literature search in two databases to identify studies which performed serological testing for autoantibodies in esophageal cancer patients and controls. Data on study characteristics and results were extracted independently by two reviewers. Overall, 45 articles reporting the detection of 35 different autoantibodies met the inclusion criteria of this review. The most common antibody detection method was enzyme-linked immunosorbent assay (ELISA), and the most frequently assessed autoantibody was anti-p53, which was tested in 17 studies and for 15 studies of which a meta-analysis was conducted to comprehensively evaluate the diagnostic value. Most antibodies were assessed in only one study, and only few authors have evaluated the diagnostic value of combinations of multiple autoantibodies. For single autoantibodies, specificity was generally very high (median 98.3 %), but sensitivity was mostly rather low (median 26.7 %). For some autoantibody combinations, substantially higher sensitivity at reasonably high levels of specificity could be achieved. Development of extended and optimized multimarker panels of autoantibodies might be a promising approach for esophageal cancer early detection.

Rethinking Autoantibody Signature Panels for Cancer Diagnosis

“…The panels that have been developed to date do not have sufficient accuracy, and meta-analyses of autoantibody panels have found them to be lacking in sensitivity and specificity. 6,7 Recently, the EarlyCDT-Lung blood test (Oncimmune Ltd., Nottingham, United Kingdom) has been proposed to assess the risk for lung cancer. 8 This test is based on detection of seven autoantibodies.…”

From blood to breath: New horizons for esophageal cancer biomarkers

“…More recently, a systematic review investigated the diagnostic utility of 35 different circulating autoantibodies, both alone and in combination, as biomarkers for the early detection of esophageal cancer[39]. Although the study did not distinguish between the two esophageal cancer sub-types, the majority of the studies included in the review were esophageal squamous cell carcinoma, a greater world-wide burden of this variant compared to the adenocarcinoma sub-type[39].…”

“…Although the study did not distinguish between the two esophageal cancer sub-types, the majority of the studies included in the review were esophageal squamous cell carcinoma, a greater world-wide burden of this variant compared to the adenocarcinoma sub-type[39]. Although the vast majority of studies reviewed reported positive associations between their candidate biomarker, and esophageal cancer, with high specificity reported, the sensitivity values were generally too low to be of any clinical significance[39]. However, combinations of autoantibodies did slightly improve the median sensitivity.…”

“…However, combinations of autoantibodies did slightly improve the median sensitivity. The authors also conducted a meta-analysis on the diagnostic value of anti-p53, reporting a significant association of serum anti-p53 with esophageal cancer, with sensitivity of 91.4% and specificity of 65%[39], contrasting their previous findings for meta-analysis of anti-p53[38]. …”

Autoantibodies against glucose-regulated protein 78 as serological biomarkers in metastatic and recurrent hepatocellular carcinoma

“…Many autoimmune diseases such as systemic lupus erythematosus (SLE) [6], diabetes [7], and rheumatoid arthritis (RA) [8] have been shown to have autoantibody responses. Many nonautoimmune diseases such as cancer [9–11] also have autoantibody responses-TAAs are cellular proteins whose aberrant regulation of function is linked to malignancy. Autoantibodies stimulated by TAAs are involved in tumorigenesis.…”