Identification of tumor-associated antigens by large-scale analysis of genes expressed in human colorectal cancer

Pedro M.S. Alves, Nicole Lévy, Brian J. Stevenson, Hanifa Bouzourene, Grégory Theiler, Gabriel Bricard, Sebastien Viatte, Maha Ayyoub, Henri Vuilleumier, Jean Claude R. Givel, Donata Rimoldi, Daniel E. Speiser, C. Victor Jongeneel, Pedro J. Romero, Frédéric Lévy

Research output: Contribution to journalArticlepeer-review

Abstract

Despite the high prevalence of colon cancer in the world and the great interest in targeted anti-cancer therapy, only few tumor-specific gene products have been identified that could serve as targets for the immunological treatment of colorectal cancers. The aim of our study was therefore to identify frequently expressed colon cancer-specific antigens. We performed a large-scale analysis of genes expressed in normal colon and colon cancer tissues isolated from colorectal cancer patients using massively parallel signal sequencing (MPSS). Candidates were additionally subjected to experimental evaluation by semi-quantitative RT-PCR on a cohort of colorectal cancer patients. From a pool of more than 6000 genes identified unambiguously in the analysis, we found 2124 genes that were selectively expressed in colon cancer tissue and 147 genes that were differentially expressed to a significant degree between normal and cancer cells. Differential expression of many genes was confirmed by RT-PCR on a cohort of patients. Despite the fact that deregulated genes were involved in many different cellular pathways, we found that genes expressed in the extracellular space were significantly over-represented in colorectal cancer. Strikingly, we identified a transcript from a chromosome X-linked member of the human endogenous retrovirus (HERV) H family that was frequently and selectively expressed in colon cancer but not in normal tissues. Our data suggest that this sequence should be considered as a target of immunological interventions against colorectal cancer.

Original languageEnglish (US)
Article number11
JournalCancer Immunity
Volume8
StatePublished - Jun 27 2008

Keywords

  • Colorectal cancer
  • Gene expression profiling
  • HERVs
  • Human
  • Massively parallel signature sequencing

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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