Discovering Panel of Autoantibodies for Early Detection of Lung Cancer Based on Focused Protein Array

Abstract

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.

A Diagnostic Model With IgM Autoantibodies and Carcinoembryonic Antigen for Early Detection of Lung Adenocarcinoma

“…In our previous study, potential IgG autoantibodies were screened in 100 serum samples from LC patients and 50 sera from NCs using focused protein array based on cancer driver genes. Interestingly, higher levels of IgG autoantibodies against survivin, PIK3CA, and JAK2 were observed in LC patients than in NCs ( 19 ). Therefore, IgM autoantibodies to TSHR, ERBB2, survivin, PIK3CA, and JAK2 may also be used as potential biomarkers for LUAD.…”

“…All NCs were individuals who had a health checkup without history of cancer, pulmonary diseases, and autoimmune diseases. The sera were extracted and stored according to standard protocols ( 19 ). The study was approved by the Medical Ethics Committee of Zhengzhou University, and all the patients and NCs signed an informed consent before their participation in the study.…”

Autoantibodies - enemies, and/or potential allies?

“…O'Reilly et al (148) reported that a panel of zinc finger proteins, including ZNF346, ZNF638, ZNF700 and ZNF768, are suitable for use as capture antigens in a bloodbased autoantibody biomarker assay for colorectal cancer. Jiang et al (48) successfully developed a panel of seven autoantibodies (reactive with: TP53, NPM1, FGFR2, PIK3CA, GNA11, HIST1H3B, and TSC1) for effective early detection of lung cancer, as well as providing novel targets for lung cancer immunotherapy.…”

“…Autoantibodies are produced in the early stage of cancer by the humoral immune response, which is activated by abnormal expression of tumor-associated antigens (TAAs) ( 48 ). The presence of autoantibodies is well established as early-stage biomarkers in cancer diagnosis.…”

“…Jiang et al. ( 48 ) successfully developed a panel of seven autoantibodies (reactive with: TP53, NPM1, FGFR2, PIK3CA, GNA11, HIST1H3B, and TSC1) for effective early detection of lung cancer, as well as providing novel targets for lung cancer immunotherapy.…”