title: Evaluation of the diagnostic value of 64 simultaneously measured autoantibodies for early detection of gastric cancer.
abstract: Autoantibodies against tumor-associated antigens (TAAs) have been suggested as biomarkers for early detection of gastric cancer. However, studies that systematically assess the diagnostic performance of a large number of autoantibodies are rare. Here, we used bead-based multiplex serology to simultaneously measure autoantibody responses against 64 candidate TAAs in serum samples from 329 gastric cancer patients, 321 healthy controls and 124 participants with other diseases of the upper digestive tract. At 98% specificity, sensitivities for the 64 tested autoantibodies ranged from 0-12% in the training set and a combination of autoantibodies against five TAAs (MAGEA4 + CTAG1 + TP53 + ERBB2_C + SDCCAG8) was able to detect 32% of the gastric cancer patients at a specificity of 87% in the validation set. Sensitivities for early and late stage gastric cancers were similar, while chronic atrophic gastritis, a precursor lesion of gastric cancer, was not detectable. However, the 5-marker combination also detected 26% of the esophageal cancer patients. In conclusion, the tested autoantibodies and combinations alone did not reach sufficient sensitivity for gastric cancer screening. Nevertheless, some autoantibodies, such as anti-MAGEA4, anti-CTAG1 or anti-TP53 and their combinations could possibly contribute to the development of cancer early detection tests (not necessarily restricted to gastric cancer) when being combined with other markers.
authors.affiliation: Division of Clinical Epidemiology and Aging Research, DKFZ, Heidelberg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Werner
authors.affiliation: Division of Clinical Epidemiology and Aging Research, DKFZ, Heidelberg, Germany.
authors.forename: Hongda
authors.initials: H
authors.lastname: Chen
authors.affiliation: Division of Molecular Diagnostics of Oncogenic Infections, DKFZ, Heidelberg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Butt
authors.affiliation: Division of Molecular Diagnostics of Oncogenic Infections, DKFZ, Heidelberg, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Michel
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Phillip
authors.initials: P
authors.lastname: Knebel
authors.affiliation: Saarland Cancer Registry, Saarbrücken, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Holleczek
authors.affiliation: Department of Medical Oncology, National Center for Tumor Diseases (NCT) and Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Inka
authors.initials: I
authors.lastname: Zörnig
authors.affiliation: GMP &T cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Stefan B
authors.initials: SB
authors.lastname: Eichmüller
authors.affiliation: Department of Medical Oncology, National Center for Tumor Diseases (NCT) and Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Jäger
authors.affiliation: Division of Molecular Diagnostics of Oncogenic Infections, DKFZ, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.affiliation: Division of Molecular Diagnostics of Oncogenic Infections, DKFZ, Heidelberg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Waterboer
authors.affiliation: Division of Clinical Epidemiology and Aging Research, DKFZ, Heidelberg, Germany.|Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.|German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
mesh_terms: D000328:Adult; D000951:Antigens, Neoplasm / Q000097:blood*; D001323:Autoantibodies / Q000235:genetics; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D013274:Stomach Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000097:blood*
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D014408:Biomarkers, Tumor; C104948:CTAG1B protein, human; C095204:MAGEA4 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53