一种用于探索作为免疫和临床潜在靶点的肿瘤特异性抗原的综合性基因组方法

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. ©2012 AACR.