五个高甲基化的微小RNA基因作为卵巢癌的潜在标志物

Five Hypermethylated MicroRNA Genes as Potential Markers of Ovarian Cancer.

作者信息

Braga E A, Loginov V I, Burdennyi A M, Filippova E A, Pronina I V, Kurevlev S V, Kazubskaya T P, Kushlinskii D N, Utkin D O, Ermilova V D, Kushlinskii N E

机构信息

Research Institute of Pathology and Pathophysiology, Moscow, Russia.

Research Centre of Medical Genetics, Moscow, Russia.

出版信息

Bull Exp Biol Med. 2018 Jan;164(3):351-355. doi: 10.1007/s10517-018-3988-y. Epub 2018 Jan 9.

DOI:10.1007/s10517-018-3988-y

PMID:29313235

Abstract

MicroRNA and methylation are important epigenetic mechanisms in the pathogenesis of cancer. The role of a group of microRNA hypermethylated genes in the pathogenesis of ovarian cancer was studied and their diagnostic and prognostic potential was evaluated. Studies on a representative sample of 54 ovarian cancer specimens with the use of methyl-specific PCR resulted in detection of five microRNA genes (MIR-9-1, MIR-9-3, MIR-107, MIR-1258, and MIR-130b) methylated in the majority of tumor specimens in comparison with paired specimens of histologically intact tissue (37-57% vs. 4-9%, p<0.01). Methylation of three genes (MIR-9-1, MIR-9-3, and MIR-130b) was significantly (p≤0.05) associated with the parameters of ovarian cancer progress (clinical stage, differentiation degree, tumor size, and presence of metastases). These findings attest to oncosuppressive role of the studied microRNA genes (MIR-9-1, MIR-9-3, MIR-107, MIR-1258, and MIR-130b) in the pathogenesis and progress of ovarian cancer and indicated their prognostic potential.

摘要

微小RNA和甲基化是癌症发病机制中重要的表观遗传机制。本研究探讨了一组微小RNA高甲基化基因在卵巢癌发病机制中的作用，并评估了它们的诊断和预后潜力。对54例卵巢癌标本的代表性样本进行甲基化特异性PCR研究，结果发现与配对的组织学完整组织标本相比，多数肿瘤标本中有5个微小RNA基因（MIR-9-1、MIR-9-3、MIR-107、MIR-1258和MIR-130b）发生甲基化（37 - 57% 对 4 - 9%，p<0.01）。三个基因（MIR-9-1、MIR-9-3和MIR-130b）的甲基化与卵巢癌进展参数（临床分期、分化程度、肿瘤大小和转移情况）显著相关（p≤0.05）。这些发现证明了所研究的微小RNA基因（MIR-9-1、MIR-9-3、MIR-107、MIR-1258和MIR-130b）在卵巢癌发病机制和进展中具有抑癌作用，并表明了它们的预后潜力。