Mini-Array of Multiple Tumor-associated Antigens (TAAs) in the Immunodiagnosis of Esophageal Cancer

Abstract

Sera of cancer patients may contain antibodies that react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). The present study aimed to determine whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach in esophageal cancer detection and diagnosis. Our mini-array of multiple TAAs consisted of eleven antigens, p53, pl6, Impl, CyclinB1, C-myc, RalA, p62, Survivin, Koc, CyclinD1 and CyclinE full-length recombinant proteins. Enzyme-linked immunosorbent assays (ELISA) were used to detect autoantibodies against eleven selected TAAs in 174 sera from patients with esophageal cancer, as well as 242 sera from normal individuals. In addition, positive results of ELISA were confirmed by Western blotting. In a parallel screening trial, with the successive addition of antigen to a final total of eleven TAAs, there was a stepwise increase in positive antibody reactions. The eleven TAAs were the best parallel combination, and the sensitivity and specificity in diagnosing esophageal cancer was 75.3% and 81.0%, respectively. The positive and negative predictive values were 74.0% and 82.0%, respectively, indicating that the parallel assay of eleven TAAs raised the diagnostic precision significantly. In addition, the levels of antibodies to seven antigens, comprising p53, Impl, C-myc, RalA, p62, Survivin, and CyclinD1, were significantly different in various stages of esophageal cancer, which showed that autoantibodies may be involved in the pathogenesis and progression of esophageal cancer. All in all, this study further supports our previous hypothesis that a combination of antibodies might acquire higher sensitivity for the diagnosis of certain types of cancer. A customized miniarray of multiple carefully-selected TAAs is able to enhance autoantibody detection in the immunodiagnosis of esophageal cancer and autoantibodies to TAAs might be reference indicators of clinical stage.

Elevated expression of the IGF2 mRNA binding protein 2 (IGF2BP2/IMP2) is linked to short survival and metastasis in esophageal adenocarcinoma

“…Autoantibodies against IMP2 have recently also been described to be elevated in ESCC [6, 9]. Our analysis of two large human esophageal cancer cohorts with about 60 tumor samples for gene expression and 50 tumor samples for protein expression showed strongly increased expression of IMP2 in the majority of esophageal cancer patients.…”

Association between serum anti‑ASXL2 antibody levels and acute ischemic stroke, acute myocardial infarction, diabetes mellitus, chronic kidney disease and digestive organ cancer, and their possible association with atherosclerosis and hypertension

“…NY-ESO-1, a cancer/testis antigen, was first identified by SEREX using sera from patients with esophageal squamous cell carcinoma (ESCC) (7). The SEREX method has also assisted in the identification of the p53 (8,9), RALA (10), TROP2 (11), SLc2A1/GLUT1 (12), tripartite motif-containing 21 (13), myomegalin (14), makorin 1 (15), EcSA (16) and cyclin L2 (17) proteins in EScc, the FIR/PUF60 protein (18) in colorectal carcinoma (cRc), the src-homology 3-domain GRB2-like 1 (19) and filamin C (20) proteins in glioma, and the EID3 protein for pancreatic neuroendocrine tumors (21). SEREX and protein array methods have been applied to atherosclerotic diseases and have identified autoantibodies against replication protein A2 (RPA2) (22), sclerostin domain-containing protein 1 (23), programmed cell death 11 (24), metalloproteinase 1, chromobox homolog 1 and chromobox homolog 5 for AIS (25), ribosomal protein L7 (26), ATPase, ca ++ transporting, plasma membrane 4, bone morphogenetic protein 1 (27), SH3BP5 (28) and deoxyhypusine synthase (29) for atherosclerosis; nardilysin for acute coronary syndrome (30), and tubulin beta 2c (31), insulin (32), glutamic acid decarboxylase (33), adiponectin (34) and growth arrest and dNA-damage-inducible gene 34 (35) for diabetes mellitus (dM).…”

Diagnostic Value of Serum Tumor-Associated Autoantibodies in Esophageal Cancer

“…The subject of this study is a group of serological markers associated with tumors. These tumor antigens are closely related to the generation and growth of tumors, such as the regulation of the cell cycle, the sensing of genomic abnormalities and the regulation of the REDOX system, tumor stem cells and tumor testicular antigens [10]. At the early stage of esophageal cancer development, the immune system in the body can specifically recognize a small amount of abnormal proteins expressed or secreted by tumor cells.…”

“…In this paper, the reference criteria for positive samples of serum autoantibodies are as follows: for the detection of esophageal carcinoma-related autoantibodies, if the test results for any autoantibodies are higher than its positive judgment value (cut-off value), then the sample will be regarded as positive [10,18]. According to this standard, the sensitivity, specificity, positive predictive value and negative predictive value of serum autoantibodies in esophageal cancer were calculated in fourfold tables.…”

“…Tumor-specific autoantibodies can be detected in serum samples from patients with various malignant tumors. Furthermore, different types of malignant tumors are related to specific autoantibody species [10].…”