Classifying Patients for Breast Cancer by Detection of Autoantibodies against a Panel of Conformation-Carrying Antigens

Abstract

Breast cancer (BCa) patients elicit an autoantibody response against cancer proteins, which reflects and amplifies the cellular changes associated with tumorigenesis. Detection of autoantibodies in plasma may provide a minimally invasive mechanism for early detection of BCa. To identify cancer proteins that elicit a humoral response, we generated a cDNA library enriched for BCa genes that encode membrane and secreted proteins, which are more likely to induce an antibody response compared to intracellular proteins. To generate conformation-carrying antigens that are efficiently recognized by patients’ antibodies, a eukaryotic expression strategy was established. Plasma from 200 BCa patients and 200 age-matched healthy controls were measured for autoantibody activity against 20 different antigens designed to have conformational epitopes using ELISA. A conditional logistic regression model was used to select a combination of autoantibody responses against the 20 different antigens to classify BCa patients from healthy controls. The best combination included ANGPTL4, DKK1, GAL1, MUC1, GFRA1, GRN and LRRC15; however, autoantibody responses against GFRA1, GRN and LRRC15 were inversely correlated with BCa. When the autoantibody responses against the 7 antigens were added to the base model, including age, BMI, race and current smoking status, the assay had the following diagnostic capabilities: c-stat (95% CI), 0.82 (0.78 to 0.86); sensitivity, 73%; specificity, 76%; and PLR (95% CI), 3.04 (2.34 to 3.94). The model was calibrated across risk deciles (Hosmer-Lemeshow, p = 0.13) and performed well in specific subtypes of BCa including estrogen receptor positive, HER-2 positive, invasive, in situ and tumor sizes >1 cm.

Autoantibody Signatures Combined with Epstein–Barr Virus Capsid Antigen-IgA as a Biomarker Panel for the Detection of Nasopharyngeal Carcinoma

“…The potential clinical significance of autoantibodies for screening and early detection seems to rely on searching an optimized panel of autoantibodies (16,26,27). Previous study, investigating the presence of autoantibodies to these six antigens in esophageal cancer, demonstrates that there was some overlap of reactivity between the various markers and that measurement of the autoantibody responses to p53 and NY-ESO-1 antigens was integral to the panel assays as reported here (16).…”

Tumour‐Associated Autoantibodies as Diagnostic Biomarkers for Breast Cancer: A Systematic Review and Meta‐Analysis

“…After excluding 579 non‐English articles and 1318 duplicates, 4441 articles not relevant to the topic and 58 meeting the exclusion criteria were excluded. Ultimately, 84 articles were included . A total of 196 specific tumour‐associated autoantibodies (Table S1) were reported, of which 23 specific tumour‐associated autoantibodies (Table ) had been studied more than once.…”

“…The 84 articles included participants from 27 countries (Table S1). The most studied populations were Chinese and American , followed by French , German and Italian . The earliest study was from 1982, and anti‐p53 antibody was the first tumour‐associated autoantibody to be reported in patients with BC.…”

“…The 84 articles included participants from 27 countries (Table S1). The most studied populations were Chinese [22,24,28,29,32,40,42,43,49,50,60,65,69,[92][93][94][95][96] and American [11,21,23,38,41,53,58,64,67,71,72,75,81,84], followed by French [4,25,48,52,62,73,74], German [37,55,57,59,80] and Italian [20,34,56,68,79]. The earliest study was from 1982, and anti-p53 antibody was the first tumour-associated autoantibody to be reported in patients ...…”

Mucin 1-specific B cell immune responses and their impact on overall survival in breast cancer patients

“…Currently, relevant research focuses on the elaboration of suitable tumor-associated antigen panels, which regularly contain MUC1 as one component. [33][34][35] Last but not least, MUC1 antigens may serve, too, as attractive targets for the development of antibody-based immunotherapy, vaccines and therapeutic drug inhibitors. 11,15,36 Vaccine strategies against MUC1 being systematically under investigation include DNA vaccines, peptide vaccines, glycopeptide vaccines, fusion proteins as well as recombinant vaccines delivered by various viral vectors.…”