Establishment and validation of an immunodiagnostic model for prediction of breast cancer

Abstract

Serum autoantibodies that react with tumor-associated antigens (TAAs) can be used as potential biomarkers for diagnosis of cancer. This study aims to evaluate the immunodiagnostic value of 11 anti-TAAs autoantibodies for detection of breast cancer (BC) and establish a diagnostic model for distinguishing BC from normal human controls (NHC) and benign breast diseases (BBD). Sera from 10 BC patients and 10 NHC were used to detect 11 anti-TAAs autoantibodies by western blotting. The 11 anti-TAAs autoantibodies were further assessed in 983 sera by relative quantitative enzyme-linked immunosorbent assay (ELISA). Binary logistic regression and Fisher linear discriminant analysis were conducted to establish a prediction model by using 184 BC and 184 NHC (training cohort, n = 568) and validated by leave-one-out cross-validation. Logistic regression model was selected to establish the prediction model. Results were validated using an independent validation cohort (n = 415). The five anti-TAAs (p53, cyclinB1, p16, p62, 14-3-3ξ) autoantibodies were selected to construct the model with the area under the curve (AUC) of 0.943 (95% CI, 0.919-0.967) in training cohort and 0.916 (95% CI, 0.886-0.947) in the validation cohort. In the identification of BC and BBD, AUCs were 0.881 (95% CI, 0.848-0.914) and 0.849 (95% CI, 0.803-0.894) in training and validation cohort, respectively. In summary, our study indicates that the immunodiagnostic model can distinguish BC from NHC and BC from BBD and this model may have a potential application in immunodiagnosis of breast cancer.

Anti-Cancer Auto-Antibodies: Roles, Applications and Open Issues

“…Out of the detected proteins, the highest score was for PI3K and p53 [ 96 ]. On the basis of similar evidence, researchers proposed an immunodiagnostic model for the prediction of breast cancer versus benign lesions and control [ 97 ]. Another breast cancer auto-antigen is mitochondrial nuclear retrograde regulator 1 (MNRR1), a mitochondrial protein that regulates multiple genes that function in cell migration and cancer metastasis and that is more highly expressed in cell lines derived from aggressive tumors [ 98 ].…”

Discovery and Validation of Serum Autoantibodies Against Tumor-Associated Antigens as Biomarkers in Gastric Adenocarcinoma Based on the Focused Protein Arrays

“…One hundred fifty-four human recombinant proteins provided by CDI Laboratories (Mayaguez) were used to construct the focused protein arrays (BC-BIO, Foshan, China). Among them, 143 proteins were encoded by 115 cancer driver genes (58 tumor suppressor gene and 57 oncogene) ( 16 ) and 11 proteins encoded by 10 genes which were reported to be potential biomarkers by our previous studies ( 17 , 18 ). The quality control of the focused protein arrays was described in our previous study ( 19 ).…”

Identification of Novel Autoantibodies Based on the Human Proteomic Chips and Evaluation of Their Performance in the Detection of Gastric Cancer

“…Many studies have shown that TAAbs can be detected before the diagnosis of cancer and can stay in the serum longer than tumor-associated antigens (TAAs) (13,14). TAAs and TAAbs have been reported as potential biomarkers for the early detection of cancers (15)(16)(17)(18).…”