Higher FOXP3-TSDR demethylation rates in adjacent normal tissues in patients with colon cancer were associated with worse survival.

Abstract:

BACKGROUND:The influence of natural regulatory T cells (nTregs) on the patients with colon cancer is unclear. Demethylated status of the Treg-specific demethylated region (TSDR) of the FOXP3 gene was reported to be a potential biomarker for the identification of nTregs. METHODS:The demethylation rate of the TSDR (TSDR-DMR) was calculated by using methylation-specific quantitative polymerase chain reaction (MS-qPCR) assay. The expression of TSDR-DMR and FOXP3 mRNA was investigated in various colorectal cancer cell lines. A total of 130 colon carcinoma samples were utilized to study the DMR at tumor sites (DMRT) and adjacent normal tissue (DMRN). The correlations between DMRs and clinicopathological variables of patients with colon cancer were studied. RESULTS:The TSDR-DMRs varied dramatically among nTregs (97.920 ± 0.466%) and iTregs (3.917 ± 0.750%). Significantly, DMRT (3.296 ± 0.213%) was higher than DMRN (1.605 ± 0.146%) (n = 130, p = 0.000). Higher DMRN levels were found in female patients (p = 0.001) and those with distant metastases (p = 0.017), and were also associated with worse recurrence-free survival in non-stage IV patients (low vs. high, p = 0.022). However, further Cox multivariate analysis revealed that the FOXP3-TSDR status does not have prognostic value. CONCLUSION:MS-qPCR assays of FOXP3-TSDR can efficiently distinguish nTregs from non-nTregs. Abnormal recruitment of nTregs occurs in the local tumor microenvironment. Infiltration of tissue-resident nTregs may have a negative role in anti-tumor effects in patients with colon cancer; however, this role is limited and complicated.

journal_name

Mol Cancer

journal_title

Molecular cancer

authors

Zhuo C,Li Z,Xu Y,Wang Y,Li Q,Peng J,Zheng H,Wu P,Li B,Cai S

doi

10.1186/1476-4598-13-153

subject

Has Abstract

pub_date

2014-06-18 00:00:00

pages

153

issn

1476-4598

pii

1476-4598-13-153

journal_volume

13

pub_type

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