title: An integrated genome-wide approach to discover tumor-specific antigens as potential immunologic and clinical targets in cancer.
abstract: 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.
authors.affiliation: Department of Immunology, Peking University Health Science Center, Beijing, China.
authors.forename: Qing-Wen
authors.initials: QW
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Sartor
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Han
authors.forename: Jixin
authors.initials: J
authors.lastname: Deng
authors.forename: Rakesh
authors.initials: R
authors.lastname: Ponnala
authors.forename: Jiang-Ying
authors.initials: JY
authors.lastname: Yang
authors.forename: Qing-Yun
authors.initials: QY
authors.lastname: Zhang
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Liao
authors.forename: Yi-Mei
authors.initials: YM
authors.lastname: Qu
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Liu
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Zhao
authors.forename: Yan-Hui
authors.initials: YH
authors.lastname: Yin
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiao-Song
authors.initials: XS
authors.lastname: Wang
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies / Q000379:methods*; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D046228:Microarray Analysis; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D009928:Organ Specificity / Q000235:genetics; D018511:Systems Integration
chemical_list: D000951:Antigens, Neoplasm