Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5888025 | Experimental and Molecular Pathology | 2015 | 9 Pages |
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.
Keywords
mRNABMP2LMSDFSPASS1PRMSMSPSTSSASPSmiR-34b/cMyxofibrosarcomaDNAMdm2FFPEAdenineEDTAEthylenediaminetetraacetic acidloss of heterozygositydeoxyribonucleic acidRNAribonucleic acidTranslocationUracilSCLCTumorigenesisthyminedaltonPleomorphic rhabdomyosarcomamessenger ribonucleic acidSoft tissue sarcomasUndifferentiated pleomorphic sarcomaalveolar soft part sarcomaSynovial sarcomaNon-small-cell lung cancerSmall-cell lung cancerNSCLCcytosineSAPMatrix-assisted laser desorption ionization time-of-flight mass spectrometryformalin-fixed paraffin-embeddedphosphatase and tensin homolog deleted on chromosome tenLOHLeiomyosarcomaMyxoid liposarcomaPleomorphic liposarcomaMALDI-TOF MSMethylationmouse double minute 2 homologshrimp alkaline phosphatasehematoxylin–eosinpolymerase chain reactionmethylation-specific polymerase chain reactionPCRbone morphogenetic protein 2PtenGuanineUPS
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Authors
Yuwen Xie, Peizhi Zong, Weiwei Wang, Dong Liu, Bingcheng Li, Yuanyuan Wang, Jianming Hu, Yan Ren, Yan Qi, Xiaobin Cui, Yunzhao Chen, Chunxia Liu, Feng Li,