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Classifying patients for breast cancer by detection of autoantibodies against a panel of conformation-carrying antigens.

ABSTRACT: Patients with breast cancer 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 breast cancer. To identify cancer proteins that elicit a humoral response, we generated a cDNA library enriched for breast cancer genes that encode membrane and secreted proteins, which are more likely to induce an antibody response compared with intracellular proteins. To generate conformation-carrying antigens that are efficiently recognized by patients' antibodies, a eukaryotic expression strategy was established. Plasma from 200 patients with breast cancer 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 patients with breast cancer 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 breast cancer. 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 (0.78-0.86); sensitivity, 73%; specificity, 76%; and positive likelihood ratio (95% CI), 3.04 (2.34-3.94). The model was calibrated across risk deciles (Hosmer-Lemeshow, P = 0.13) and performed well in specific subtypes of breast cancer including estrogen receptor positive, HER-2 positive, invasive, in situ and tumor sizes >1 cm.

SUBMITTER: Evans RL

PROVIDER: S-EPMC4437507 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Classifying patients for breast cancer by detection of autoantibodies against a panel of conformation-carrying antigens.

Evans Rick L RL Pottala James V JV Egland Kristi A KA

Cancer prevention research (Philadelphia, Pa.) 20140318 5

Patients with breast cancer 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 breast cancer. To identify cancer proteins that elicit a humoral response, we generated a cDNA library enriched for breast cancer genes that encode membrane and secreted proteins, which are more likely to induce an antibody respon ...[more]

PMID: 24641868

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Project description:BackgroundAutoantibody-mediated psychiatric disorder is often difficult to diagnose as the clinical features of psychiatric disorder associated with neural autoantibodies are often similar. Thus, it is of major relevance to investigate whether psychopathology can differentiate between both disease entities as a biomarker and help us in searching for specific autoantibodies associated with psychiatric symptoms.MethodsWe enrolled 154 patients of the Department of Psychiatry and Psychotherapy of the University Medical Center Göttingen with psychopathology data and retrospectively evaluated their patient records using the classification systems AMDP (Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie) and HiTOP (Hierarchical Taxonomy of Psychopathology).ResultsWe identified 35 psychiatric patients revealing autoantibodies in their serum and/or cerebrospinal fluid (CSF) and 119 with no autoantibodies. Relying on the AMDP system, many more psychiatric patients with serum autoantibodies (51%) had problems with orientation than those without autoantibodies (32%) (p < 0.05). Furthermore, fewer psychiatric patients with serum autoantibodies exhibited a blunted affect (11.4 vs. 32.8%, p < 0.01) and affective rigidity (20 vs. 45%, p < 0.01). In particular, psychiatric patients presenting CSF autoantibodies (indicating an autoimmune symptomatic basis) experience more loss of vitality (5%) than those without autoantibodies (0%) (p < 0.05). Another interesting finding is that according to the AMDP classification, a manic syndrome is much more frequent in autoantibody-positive (8.6%) than autoantibody-negative psychiatric patients (0.8%) (p < 0.05). Another aspect is the more frequent occurrence of attention and memory deficits in patients with autoantibodies against intracellular targets compared with targets on the membrane surface.ConclusionOur findings indicate that neural autoantibodies in psychiatric patients could indicate a phenotype more often characterized by a manic syndrome, orientation disturbances within the cognitive spectrum, and fewer affect disturbances characterized by less blunted affect and not as seriously impaired feelings of vitality compared to controls. The novelty of our approach is the extensive autoantibody tests for various psychiatric syndromes in combination with a profound psychometric measurement with two different scales.

Dataset Information

Classifying patients for breast cancer by detection of autoantibodies against a panel of conformation-carrying antigens.

Publications

Classifying patients for breast cancer by detection of autoantibodies against a panel of conformation-carrying antigens.

Similar Datasets

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