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.
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Authors | Changhua Zhuo, Zhiyuan Li, Ye Xu, Yuwei Wang, Qingguo Li, Junjie Peng, Hongtu Zheng, Peng Wu, Bin Li, Sanjun Cai |
Journal | Molecular cancer
(Mol Cancer)
Vol. 13
Pg. 153
(Jun 18 2014)
ISSN: 1476-4598 [Electronic] England |
PMID | 24938080
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- FOXP3 protein, human
- Forkhead Transcription Factors
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Topics |
- Aged
- Colonic Neoplasms
(genetics, metabolism, pathology)
- DNA Methylation
(genetics)
- Female
- Forkhead Transcription Factors
(genetics)
- Humans
- Male
- Middle Aged
- Prognosis
- Survival Analysis
- T-Lymphocytes, Regulatory
(metabolism)
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