期刊
MOLECULAR CANCER
卷 13, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1476-4598-13-153
关键词
Regulatory T cells; Colorectal cancer; Transcription factor forkhead box P3; Treg-specific demethylated region; Survival analysis; Cox regression
资金
- National Natural Science Foundation of China [81372646, 81330072, 31370863]
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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