title: 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.
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Peizhi
authors.initials: P
authors.lastname: Zong
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Bingcheng
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China; Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China, Shihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China; Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China, Shihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China; Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China, Shihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China; Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China, Shihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China; Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China, Shihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Yunzhao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China; Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China, Shihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China. Electronic address: liuliu2239@sina.com.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China; Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China, Shihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China. Electronic address: lifeng7855@126.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D012509:Sarcoma / Q000175:diagnosis / Q000378:metabolism*; D012983:Soft Tissue Neoplasms / Q000175:diagnosis / Q000235:genetics*
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs
keywords: Methylation; MircroRNA-34b/c; Soft tissue sarcomas; Translocation; Tumorigenesis