Discovering Panel of Autoantibodies for Early Detection of Lung Cancer Based on Focused Protein Array.
Di Jiang, Xue Zhang, Man Liu, Yulin Wang, Tingting Wang, Lu Pei, Peng Wang, Hua Ye, Jianxiang Shi, Chunhua Song, Kaijuan Wang, Xiao Wang, Liping Dai, Jianying Zhang
Author Information
Di Jiang: Department of Oncology, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Xue Zhang: Department of Oncology, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Man Liu: Department of Oncology, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Yulin Wang: Department of Oncology, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Tingting Wang: Department of Clinical Laboratory, Fuwai Central China Cardiovascular Hospital, Zhengzhou, China.
Lu Pei: Department of Clinical Laboratory, Zhengzhou Hospital of Traditional Chinese Medicine, Zhengzhou, China.
Peng Wang: Henan Key Laboratory of Tumor Epidemiology & State Key Laboratory of Esophageal Cancer Prevention, Zhengzhou University, Zhengzhou, China.
Hua Ye: Henan Key Laboratory of Tumor Epidemiology & State Key Laboratory of Esophageal Cancer Prevention, Zhengzhou University, Zhengzhou, China.
Jianxiang Shi: Department of Oncology, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Chunhua Song: Henan Key Laboratory of Tumor Epidemiology & State Key Laboratory of Esophageal Cancer Prevention, Zhengzhou University, Zhengzhou, China.
Kaijuan Wang: Henan Key Laboratory of Tumor Epidemiology & State Key Laboratory of Esophageal Cancer Prevention, Zhengzhou University, Zhengzhou, China.
Xiao Wang: Department of Oncology, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Liping Dai: Department of Oncology, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Jianying Zhang: Department of Oncology, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Substantial studies indicate that autoantibodies to tumor-associated antigens (TAAbs) arise in early stage of lung cancer (LC). However, since single TAAbs as non-invasive biomarkers reveal low diagnostic performances, a panel approach is needed to provide more clues for early detection of LC. In the present research, potential TAAbs were screened in 150 serum samples by focused protein array based on 154 proteins encoded by cancer driver genes. Indirect enzyme-linked immunosorbent assay (ELISA) was used to verify and validate TAAbs in two independent datasets with 1,054 participants (310 in verification cohort, 744 in validation cohort). In both verification and validation cohorts, eight TAAbs were higher in serum of LC patients compared with normal controls. Moreover, diagnostic models were built and evaluated in the training set and the test set of validation cohort by six data mining methods. In contrast to the other five models, the decision tree (DT) model containing seven TAAbs (TP53, NPM1, FGFR2, PIK3CA, GNA11, HIST1H3B, and TSC1), built in the training set, yielded the highest diagnostic value with the area under the receiver operating characteristic curve (AUC) of 0.897, the sensitivity of 94.4% and the specificity of 84.9%. The model was further assessed in the test set and exhibited an AUC of 0.838 with the sensitivity of 89.4% and the specificity of 78.2%. Interestingly, the accuracies of this model in both early and advanced stage were close to 90%, much more effective than that of single TAAbs. Protein array based on cancer driver genes is effective in screening and discovering potential TAAbs of LC. The TAAbs panel with TP53, NPM1, FGFR2, PIK3CA, GNA11, HIST1H3B, and TSC1 is excellent in early detection of LC, and they might be new target in LC immunotherapy.
