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Hypermethylation of potential tumor suppressor miR-34b/c is correlated with late clinical stage in patients with soft tissue sarcomas.

Abstract：

:Soft tissue sarcomas (STSs) are comparatively rare malignant tumors with poor prognosis. STSs predominantly arise from mesenchymal differentiation. MicroRNA-34b/c, the transcriptional targets of tumor suppressor p53, possesses tumor suppressing property. Hypermethylation of miR-34b/c has been associated with tumorigenesis and the progression of various cancers. To determine whether aberrant miR-34b/c methylation occurs in STSs, we quantitatively evaluated the methylation level of miR-34b/c in 57 STS samples and 20 cases of peripheral blood from healthy volunteers serving as normal controls by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. We found that miRNA34b/c is more frequently methylated in STSs (0.157±0.028) than in normal controls (0.098±0.012, p=0.038). Furthermore, the methylation levels of CpG_1.2.3, CpG_4.5.6.7, and CpG_11.12.13 of miR-34b/c were significantly higher in the STS group than in the normal control group (p<0.001). No significant differences in the methylation levels within miR-34b/c were observed between specific reciprocal translocations in STSs and nonspecific reciprocal translocations in STSs (0.146±0.039 vs. 0.168±0.035, p>0.05). The methylation levels of miR-34b/c in STSs were associated with clinical stage. The methylation levels of CpG_1.2.3, CpG_4.5.6.7, CpG_9.10, CpG_11.12.13, and CpG_14 in tumor-stage III/IV tissues were significantly higher than those in tumor-stage I/II tissues. Our findings indicated that DNA hypermethylation of the miR-34b/c is a relatively common event in STSs and is significantly correlated with late clinical stage in patients with STSs. Hypermethylation of the miR-34b/c may be pivotal in the oncogenesis and progression of STSs and may be a potential prognostic factor for STSs.

journal_name

Exp Mol Pathol

journal_title

Experimental and molecular pathology

authors

Xie Y,Zong P,Wang W,Liu D,Li B,Wang Y,Hu J,Ren Y,Qi Y,Cui X,Chen Y,Liu C,Li F

doi

10.1016/j.yexmp.2015.03.017

subject

Has Abstract

pub_date

2015-06-01 00:00:00

pages

446-54

issue

eissn

0014-4800

issn

1096-0945

pii

S0014-4800(15)00052-0

journal_volume

pub_type

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Hypermethylation of potential tumor suppressor miR-34b/c is correlated with late clinical stage in patients with soft tissue sarcomas.