Identification of the Antigens Recognised by Colorectal Cancer Patients Using Sera from Patients Who Exhibit a Crohn's-like Lymphoid Reaction

Biomolecules. 2022 Jul 29;12(8):1058. doi: 10.3390/biom12081058.

Abstract

A Crohn’s-like lymphoid reaction (CLR) is observed in about 15% of colorectal cancer (CRC) patients and is associated with favourable outcomes. To identify the immune targets recognised by CRC CLR patient sera, we immunoscreened a testes cDNA library with sera from three patients. Immunoscreening of the 18 antigens identified by SEREX with sera from normal donors showed that only the heavy chain of IgG3 (IGHG3) and a novel antigen we named UOB-COL-7, were solely recognised by sera from CRC CLR patients. ELISA showed an elevation in IgG3 levels in patients with CRC (p = 0.01). To extend our studies we analysed the expression of our SEREX-identified antigens using the RNA-sequencing dataset (GSE5206). We found that the transcript levels of multiple IGHG probesets were highly significant (p < 0.001) in their association with clinical features of CRC while above median levels of DAPK1 (p = 0.005) and below median levels of GTF2H5 (p = 0.004) and SH3RF2 (p = 0.02) were associated with improved overall survival. Our findings demonstrate the potential of SEREX-identified CRC CLR antigens to act as biomarkers for CRC and provide a rationale for their further characterization and validation.

Keywords: SEREX; colon cancer; crohn’s-like lymphoid reaction (CLR); immunoglobulin heavy chain; immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics
  • Colorectal Neoplasms*
  • Crohn Disease* / genetics
  • Gene Library
  • Humans
  • Immunoglobulin G / genetics
  • Oncogene Proteins / genetics

Substances

  • Carrier Proteins
  • Immunoglobulin G
  • Oncogene Proteins
  • SH3RF2 protein, human

Grants and funding

This work was funded by Breakthrough Cancer Research (previously known as Cork Cancer Research Centre) while the University of Bedfordshire awarded a fee waiver to V.B.B. for her MPhil studies that formed the basis of this publication.