The Immunome of Colon Cancer: Functional In Silico Analysis of Antigenic Proteins Deduced from IgG Microarray Pro?ling  

作　　者：Johana A. Luna Coronell Khulan Sergelen Philipp Hofe Istvan Gyurjan Stefanie Brezina Peter Hettegger Gernot Leeb Karl Mach Andrea Gsur Andreas Weinhausel 

机构地区：[1]Molecular Diagnostics, AIT - Austrian Institute of Technology, A-1190 Vienna, Austria [2]Department of Medicine I, Institute of Cancer Research, Comprehensive Cancer Center, Medical University Vienna, A-1090 Vienna, Austria [3]Hospital Oberpullendorf, A-7350, Oberpullendorf, Austria

出　　处：《Genomics, Proteomics & Bioinformatics》2018年第1期73-84,共12页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported by the Life Science Krems Fund (Project No. 30);Jubilumsfonds of the Austrian National Bank (Project No. 15192);Vienna Science and Technology Fund (Project No LS11-026) of Austria

摘　　要：Characterization of the colon cancer immunome and its autoantibody signature from differentially-reactive antigens （DIRAGs） could provide insights into aberrant cellular mechanisms or enriched networks associated with diseases. The purpose of this study was to characterize the antibody profile of plasma samples from 32 colorectal cancer （CRC） patients and 32 controls using proteins isolated from 15,417 human cDNA expression clones on microarrays. 671 unique DIRAGs were identified and 632 were more highly reactive in CRC samples. Bioinformatics analyses reveal that compared to control samples, the immunoproteomic IgG profiling of CRC samples is mainly associated with cell death, survival, and proliferation pathways, especially proteins involved in EIF2and mTOR signaling. Ribosomal proteins （e.g., RPL7, RPL22, and RPL27A） and CRC-related genes such as APC, AXIN1, E2F4, MSH2, PMS2, and TP53 were highly enriched. In addition, dif- ferential pathways were observed between the CRC and control samples. Furthermore, 103 DIR- AGs were reported in the SEREX antigen database, demonstrating our ability to identify known and new reactive antigens. We also found an overlap of 7 antigens with 48 ＂CRC genes.＂ These data indicate that immunomies profiling on protein mieroarrays is able to reveal the complexity of immune responses in cancerous diseases and faithfully reflects the underlying pathology.Characterization of the colon cancer immunome and its autoantibody signature from differentially-reactive antigens （DIRAGs） could provide insights into aberrant cellular mechanisms or enriched networks associated with diseases. The purpose of this study was to characterize the antibody profile of plasma samples from 32 colorectal cancer （CRC） patients and 32 controls using proteins isolated from 15,417 human cDNA expression clones on microarrays. 671 unique DIRAGs were identified and 632 were more highly reactive in CRC samples. Bioinformatics analyses reveal that compared to control samples, the immunoproteomic IgG profiling of CRC samples is mainly associated with cell death, survival, and proliferation pathways, especially proteins involved in EIF2and mTOR signaling. Ribosomal proteins （e.g., RPL7, RPL22, and RPL27A） and CRC-related genes such as APC, AXIN1, E2F4, MSH2, PMS2, and TP53 were highly enriched. In addition, dif- ferential pathways were observed between the CRC and control samples. Furthermore, 103 DIR- AGs were reported in the SEREX antigen database, demonstrating our ability to identify known and new reactive antigens. We also found an overlap of 7 antigens with 48 ＂CRC genes.＂ These data indicate that immunomies profiling on protein mieroarrays is able to reveal the complexity of immune responses in cancerous diseases and faithfully reflects the underlying pathology.

关 键 词：Autoantibody tumorbiomarker Cancer immunology Colorectal cancer IMMUNOMICS Protein microarray 

分 类 号：R735.34[医药卫生—肿瘤]