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

Johana A Luna Coronell,Khulan Sergelen,Philipp Hofer,István Gyurján,Stefanie Brezina,Peter Hettegger,Gernot Leeb,Karl Mach,Andrea Gsur,Andreas Weinhäusel

doi:10.1016/j.gpb.2017.10.002

Abstract

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 EIF2 and 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, differential pathways were observed between the CRC and control samples. Furthermore, 103 DIRAGs 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 immunomics profiling on protein microarrays is able to reveal the complexity of immune responses in cancerous diseases and faithfully reflects the underlying pathology.

Highlights

Colorectal cancer (CRC) is reported worldwide as the second most common cancer in women and third in men, which makes it a leading cause of cancer-associated mortality in developed countries [1,2]
To identify differentially-reactive antigens (DIRAGs) from IgG profiling, we performed the immunoprofiling of CRC and control samples using our inhouse protein microarray as previously described [36]
Comparing the resulting list with the list of DIRAGs, we found an overlap of 7 antigens between the published CRC tumor-associated antigens (TAAs) and the DIRAGs (Table 3)

Summary

Introduction

Colorectal cancer (CRC) is reported worldwide as the second most common cancer in women and third in men, which makes it a leading cause of cancer-associated mortality in developed countries [1,2]. Various screening methods for CRC are available, such as fecal occult blood tests (FOBT), colonoscopy, and flexible sigmoidoscopy [3]. Implementation of nationwide screening programs, and minimal invasive and early diagnostic methods could help to reduce the high mortality rate of CRC. Diagnostic methods would enable prompt detection of cancer at early stages, which is essential for therapeutic success and a higher patient survival rate. Discovery, and identification of sensitive as well as specific markers that could be exploited at the earliest possible stage is needed. The identification of biomarkers shall be established with easy sample access [4] from body fluids like serum, plasma or saliva in a minimally invasive manner, which are generally preferred than undergoing colonoscopy

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