Identification of a panel of complex autoantigens (LGALS3, PHB2, MUC1, and GK2) in combination with CA15-3 for the diagnosis of early-stage breast cancer

Xiaoxiao Zuo, Ling Chen, Lifeng Liu, Zhe Zhang, Xiaojin Zhang, Qing Yu, Lu Feng, Xinhan Zhao, Tianjie Qin

Currently, there is no effective single antigen and there are only a very limited number of complex antigens for the diagnosis of early-stage breast cancer (BC). In this study, we used serological analysis of recombinant cDNA expression libraries (SEREX) in combination with phage display technology to screen complex autoantigens from the sera of BC patients. The cDNA expression library was constructed using tissue samples of three patients with BC at as early as stage T1N0M0. The serum samples of ten patients, including the three patients who provided tissue samples, as well as five healthy human subjects as controls were used to screen the library. All seven autoantigens were identified from the library by four rounds of screening and matched the existing genes after a blast search using NCBI-BLAST. Then, the expression conditions of the autoantibodies of the seven autoantigens and anti-CA15-3 in the sera from 100 BC patients and 50 healthy donors were examined by gray values. The data were analyzed by the area under the receiver operating characteristic (ROC) curve and logistic regression diagnostic models. In the end, a panel of complex autoantigens consisting of B11 (LGALS3), B18 (PHB2), B119 (MUC1), B130 (GK2), and CA15-3, which had a sensitivity of 87 % and a specificity of 76 %, were identified. The area under the curve (AUC) of the complex antigens was 0.872, which is significantly greater than that of anti-CA15-3 alone (AUC = 0.634) for the diagnosis of BC. Thus, this panel of complex antigens provides a promising strategy for the diagnosis of early-stage BC.