Identification of tumor-associated antigens of lung cancer: SEREX combined with bioinformatics analysis.

Abstract

The aim of this study is to identify novel tumor-associated antigens (TAAs) of lung cancer by using serological analysis of recombinant cDNA expression library (SEREX) and bioinformatics analysis as well as to explore their humoral immune response. SEREX and pathway enrichment analysis were used to immunoscreen TAAs of lung cancer and elaborate their function in biological pathways, respectively. Subsequently, the sera level of autoantibodies against the selected TAAs (TOP2A, TRIM37, HSP90AB1, EEF1G and TPP1) was detected by immunoserological analysis to explore the immune response of these antigens. The Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) database were applied to explore the mRNA and protein expression level of TOP2A, TRIM37 and HSP90AB1 in tissues, respectively. Seventy positive clones were identified by SEREX which contain 63 different genes, and 35 genes of them have been reported. These 35 genes were mainly related to regulation of different transcription factor and performed enrichment in legionellosis, RNA transport, IL-17 signaling pathway via enrichment analysis. Additionally, the positive rate of autoantibodies against TOP2A, TRIM37 and HSP90AB1 in lung cancer patients were typically higher than normal control (NC; P < 0.05). Moreover, the combination of the autoantibodies against TOP2A, TRIM37 and HSP90AB1 possessed an excellent diagnostic performance with sensitivity of 84% and specificity of 60%. The mRNA expression level of TOP2A was obviously unregulated in squamous cell carcinoma (SCC) tissues and adenocarcinoma (ADC) tissues compared to normal tissues (P < 0.05). In addition, TRIM37 and HSP90AB1 also showed a significant difference between SCC and NC at the mRNA expression level (P < 0.05). This study combining comprehensive autoantibody and gene expression assays has added to the growing list of lung cancer antigens, which may aid the development of diagnostic and immunotherapeutic targets for lung cancer patients.

• Authors: Yulin Wang, Peng Wang, Man Liu, Xue Zhang, Qiufang Si, Ting Yang, Hua Ye, Chunhua Song, Jianxiang Shi, Kaijuan Wang, Xiao Wang, Jianying Zhang, Liping Dai
• Journal: Journal of immunological methods (J Immunol Methods) Vol. 492 Pg. 112991 (05 2021) ISSN: 1872-7905 [Electronic] Netherlands
• PMID: 33587914 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't, Validation Study)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Antigens, Neoplasm
• Autoantibodies
• Biomarkers, Tumor
• HSP90 Heat-Shock Proteins
• HSP90AB1 protein, human
• Poly-ADP-Ribose Binding Proteins
• Tripartite Motif Proteins
• Tripeptidyl-Peptidase 1
• TRIM37 protein, human
• Ubiquitin-Protein Ligases
• TPP1 protein, human
• DNA Topoisomerases, Type II
• TOP2A protein, human

Topics

• Adenocarcinoma of Lung (blood, diagnosis, genetics, immunology)
• Adult
• Aged
• Antigens, Neoplasm (genetics, immunology)
• Autoantibodies (blood, immunology)
• Biomarkers, Tumor (blood, immunology)
• Carcinoma, Squamous Cell (blood, diagnosis, genetics, immunology)
• Case-Control Studies
• Computational Biology
• DNA Topoisomerases, Type II (genetics, immunology)
• Datasets as Topic
• Diagnosis, Differential
• Female
• Gene Expression Profiling
• Gene Library
• HSP90 Heat-Shock Proteins (genetics, immunology)
• Healthy Volunteers
• Humans
• Lung Neoplasms (blood, diagnosis, genetics, immunology)
• Male
• Middle Aged
• Poly-ADP-Ribose Binding Proteins (genetics, immunology)
• Sensitivity and Specificity
• Serologic Tests (methods)
• Tripartite Motif Proteins (genetics, immunology)
• Tripeptidyl-Peptidase 1
• Ubiquitin-Protein Ligases (genetics, immunology)
• Young Adult