CD80 down-regulation is associated to aberrant DNA methylation in non-inflammatory colon carcinogenesis

Marco Scarpa, Melania Scarpa, Ignazio Castagliuolo, Francesca Erroi, Silvia Basato, Paola Brun, Imerio Angriman, Carlo Castoro

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: The lack of positive costimulatory molecules represents one of the mechanisms by which tumor cells evade immune surveillance. Promoter hypermethylation plays a major role in cancer development through transcriptional silencing of critical genes. The aim of this study was to examine the expression of the costimulatory molecule CD80 in relationship with genomic methylation in non-inflammatory colon carcinogenesis. Methods: Colonic mucosal samples were collected from healthy subjects (n = 30) and from dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b and CD80 mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. CD80 expression was assessed in HT29, HCT-15 and LoVo cell lines after treatment with the DNA-methyltransferase inhibitor 5-Aza-2'-deoxycytidine. Results: CD80 mRNA levels were significantly lower in the non-inflammatory dysplastic colonic mucosa of patients with one or more methylated genes and inversely correlated with patients' methylation scores (τ = -0.41, p = 0.05 and τ = -0.37, p = 0.05, respectively). Treatment with 5-Aza-2'-deoxycytidine significantly increased CD80 expression both in terms of the level of CD80 mRNA (p = 0.007) and of CD80+ cells (p = 0.003). Conclusions: These results indicate that the failure of immune surveillance mechanisms in non-inflammatory colon carcinogenesis may be linked to genomic methylation directly or indirectly affecting CD80 expression.

Original languageEnglish
Article number388
Pages (from-to)1-8
Number of pages8
JournalBMC Cancer
Volume16
Issue number1
DOIs
Publication statusPublished - Jul 4 2016

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DNA Methylation
Methylation
decitabine
Colon
Carcinogenesis
Down-Regulation
Messenger RNA
Methyltransferases
Gene Silencing
Adenoma
Genes
Real-Time Polymerase Chain Reaction
Neoplasms
Healthy Volunteers
Mucous Membrane
Adenocarcinoma
Cell Line
Polymerase Chain Reaction
DNA
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

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CD80 down-regulation is associated to aberrant DNA methylation in non-inflammatory colon carcinogenesis. / Scarpa, Marco; Scarpa, Melania; Castagliuolo, Ignazio; Erroi, Francesca; Basato, Silvia; Brun, Paola; Angriman, Imerio; Castoro, Carlo.

In: BMC Cancer, Vol. 16, No. 1, 388, 04.07.2016, p. 1-8.

Research output: Contribution to journalArticle

Scarpa, Marco ; Scarpa, Melania ; Castagliuolo, Ignazio ; Erroi, Francesca ; Basato, Silvia ; Brun, Paola ; Angriman, Imerio ; Castoro, Carlo. / CD80 down-regulation is associated to aberrant DNA methylation in non-inflammatory colon carcinogenesis. In: BMC Cancer. 2016 ; Vol. 16, No. 1. pp. 1-8.
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