Tracking the antibody immunome in sporadic colorectal cancer by using antigen self-assembled protein arrays

María González-González, José María Sayagués, Luis Muñoz-Bellvís, Carlos Eduardo Pedreira, Marcello L.R. de Campos, Jacinto García, José Antonio Alcázar, Patrick F. Braz, Breno L. Galves, Luis Miguel González, Oscar Bengoechea, María Del Mar Abad, Juan Jesús Cruz, Lorena Bellido, Emilio Fonseca, Paula Díez, Pablo Juanes-Velasco, Alicia Landeira-Viñuela, Quentin Lecrevisse, Enrique MontalvilloRafael Góngora, Oscar Blanco, José Manuel Sánchez-Santos, Joshua Labaer, Alberto Orfao, Manuel Fuentes

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (n = 38) and metastatic (n = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.

Original languageEnglish (US)
Article number2718
JournalCancers
Volume13
Issue number11
DOIs
StatePublished - Jun 1 2021
Externally publishedYes

Keywords

  • Auto-antibody profiling
  • Colorectal cancer
  • Immunomics
  • Metastases
  • NAPPArrays
  • Protein antigen array
  • Tumor-associated antigen proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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