An integrated genome-wide approach to discover tumor specific antigens as potential immunological and clinical targets in cancer
| Autor: | Dong Mei Han, Qing Yun Zhang, Maureen A. Sartor, Yanhui Yin, Yue Wang, Jiang Ying Yang, Xiaosong Wang, Hong Mei Zhao, Lu Li, Wei Feng Chen, Qingwen Xu, Fang Fang Liu, Wei Zhao, Yi mei Qu, Jixin Deng, Yu Zhang, Rakesh Ponnala, Guo qing Liao |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Cancer Research Computational biology Biology Genome Article Antigen Antigens Neoplasm Neoplasms medicine Humans Molecular Targeted Therapy Gene Genetic Association Studies Microarray analysis techniques Gene Expression Profiling Autoantibody Cancer Genomics medicine.disease Microarray Analysis Gene expression profiling Gene Expression Regulation Neoplastic Systems Integration Oncology Organ Specificity Case-Control Studies Immunology Human genome Female Immunotherapy Genome-Wide Association Study |
| Popis: | Tumor-specific antigens (TSA) are central elements in the immune control of cancers. To systematically explore the TSA genome, we developed a computational technology called heterogeneous expression profile analysis (HEPA), which can identify genes relatively uniquely expressed in cancer cells in contrast to normal somatic tissues. Rating human genes by their HEPA score enriched for clinically useful TSA genes, nominating candidate targets whose tumor-specific expression was verified by reverse transcription PCR (RT-PCR). Coupled with HEPA, we designed a novel assay termed protein A/G–based reverse serological evaluation (PARSE) for quick detection of serum autoantibodies against an array of putative TSA genes. Remarkably, highly tumor-specific autoantibody responses against seven candidate targets were detected in 4% to 11% of patients, resulting in distinctive autoantibody signatures in lung and stomach cancers. Interrogation of a larger cohort of 149 patients and 123 healthy individuals validated the predictive value of the autoantibody signature for lung cancer. Together, our results establish an integrated technology to uncover a cancer-specific antigen genome offering a reservoir of novel immunologic and clinical targets. Cancer Res; 72(24); 6351–61. ©2012 AACR. |
| Databáze: | OpenAIRE |
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