DNA启动子甲基化与白血病的关系

甲基化修饰是哺乳动物DNA的一种正常自然修饰方式,在基因表达的调控、基因结构的稳定等方面有重要作用。异常甲基化,尤其是启动子高甲基化在白血病的发生发展过程中起重要作用。甲基化研究可用于抑癌基因的筛选、微小残留病灶的检测及预后判断,去甲基化治疗已成为白血病治疗的又一重要途径。本文就近年来白血病异常甲基化在白血病机制研究、诊断及治疗中的应用等方面的研究进展作一综述。     

DNA甲基化调控的MicroRNA在乳腺癌中的研究进展

微小核糖核酸(miRNA)是一类内源性非编码小RNA, 长约18~25个核苷酸, 其通过与特定靶mRNA结合来抑制mRNA翻译过程, 从而在转录后水平调节靶基因的表达水平, 与恶性肿瘤的发生、发展、侵袭以及转移密切相关。前期大量研究发现, DNA甲基化可能是调控乳腺癌中miRNA表达异常的机制, 包括癌基因miRNA低甲基化激活和抑癌基因miRNA高甲基化失活, 从而导致miRNA调控的下游靶基因表达异常, 参与乳腺癌的发生发展。因此, 本文主要就DNA甲基化调控的miRNA在乳腺癌中的研究进展作一综述。     

DNA启动子甲基化与白血病的关系

甲基化修饰是哺乳动物DNA的一种正常自然修饰方式，在基因表达的调控、基因结构的稳定等方面有重要作用。异常甲基化，尤其是启动子高甲基化在白血病的发生发展过程中起重要作用。甲基化研究可用于抑癌基因的筛选、微小残留病灶的检测及预后判断，去甲基化治疗已成为白血病治疗的又一重要途径。本文就近年来白血病异常甲基化在白血病机制研究、诊断及治疗中的应用等方面的研究进展作一综述。     

骨髓增生异常综合征患者血浆DNA中FHIT基因启动子区甲基化状态及地西他滨的去甲基化作用

本研究旨在检测骨髓增生异常综合征(MDS)患者血浆DNA中FHIT基因启动子区域甲基化状况及地西他滨对其甲基化的影响。采用甲基化特异性聚合酶链反应法检测1例初治的MDS患者、3例MDS转化而来的AML患者在地西他滨序贯半量CAG方案化疗前后血浆DNA中FHIT基因启动子区域CPG岛甲基化情况,并分析其临床疗效。结果表明,3例患者治疗前有FHIT基因甲基化。治疗1个疗程后其中2例患者FHIT基因甲基化得到逆转,4例患者中有2例获得临床缓解,2例无效。结论:MDS的发生可能与FHIT基因甲基化相关,地西他滨对MDS患者血浆DNA中FHIT基因高甲基化具有明显的去甲基化作用。血浆DNA的FHIT基因甲基化检测可能成为MDS辅助诊断和预后判断的分子标记。     

长链非编码RNA在乳腺癌中的研究进展

研究发现长链非编码RNA(long non-coding RNA,LncRNA)表达异常与乳腺癌发生、发展和转移密切相关。深入研究LncRNA在乳腺癌中的作用及机制有望为乳腺癌诊断和治疗提供新的分子靶点。本文就LncRNA在乳腺癌中的作用、机制和潜在临床应用价值作一综述。     

抑癌因子DNA高甲基化与肿瘤

肿瘤DNA甲基化的异常包括基因组整体甲基化水平降低或和某些基因启动子区域甲基化水平异常升高。前者可导致原癌基因活化及基因组不稳定等,而基因启动子区域发生异常高甲基化则可导致基因转录沉默,使重要基因如抑癌基因等低表达或不表达及增加点突变,并通过影响多条细胞信号转导通路来干预细胞周期和细胞凋亡等,从而影响肿瘤的发生发展及预后和治疗。了解抑癌因子DNA高甲基化与肿瘤的研究现状,可望为揭示肿瘤发生机制提供新的思路,为肿瘤诊断和治疗提供新的标记物和靶点。     

DNA甲基化与肺癌临床关系研究进展

DNA异常甲基化是一种表观遗传学改变,与肿瘤临床关系是目前肿瘤分子生物学研究的热点,常发生在启动子区的CpG岛,与肺癌发生密切相关,是肺癌发生中的早期事件。DNA甲基化是非小细胞肺癌（NSCLC）诊断、分期及治疗预后特异性较强的标识物。最近研究表明某些基因甲基化发生在CpA,CpC,CpT二核苷酸区,即non-CpG岛。     

ID4基因高甲基化与乳腺癌相关性研究

目的观察乳腺癌中DNA结合抑制因子4(ID4)基因启动子区甲基化状态及其与临床病理特征间的关系,探讨ID4基因在乳腺癌发病过程中的作用机制。方法采用焦磷酸测序法定量检测乳腺癌及正常组织标本中ID4基因启动子区甲基化水平,并分析其在不同临床病理特征间的差异;用RT-PCR检测MM-453细胞去甲基化处理前后ID4启动子区甲基化水平及mRNA表达情况。结果乳腺癌组织中ID4启动子区甲基化水平显著高于正常乳腺组织[(31.16±1.50)%vs(19.89±0.22)%,P0.01];ER+乳腺癌组织中ID4甲基化水平显著高于ER-乳腺癌组织[(36.57±1.97)%vs(27.91±1.83)%,P0.01];去甲基化处理后MM-453细胞ID4甲基化水平明显下降,mRNA表达显著上升,两者呈负相关(r=-0.973,P0.01)。结论 ID4基因可能通过启动子区高甲基化等多种途径在乳腺癌发生、发展过程中起着重要作用,其启动子区高甲基化在ER+的乳腺癌中具有重要意义。     

DNA甲基化定量检测的新方法:甲基化敏感性高分辨率熔解分析

DNA甲基化被认为是新一代的肿瘤标志,其对肿瘤风险评估、早期诊断以及肿瘤预后都有极其重要的诊断价值,MS-HRM方法 是一种新的定量检测甲基化的方法 ,它是基于亚硫酸盐对DNA进行修饰后具有不同的碱基构成,导致甲基化和非甲基化模板扩增后的产物热稳定性不同而进行检测.本文阐述了该方法 在肿瘤和遗传性疾病检测中的应用及优点,并对其在临床分子检测中的应用前景进行了展望.     

DNA甲基化及其在肿瘤分子诊断中的前景

DNA甲基化是研究最为深入的表观遗传学机制。该机制的异化可导致基因表达的异常及基因组稳定性的降低，继而促进肿瘤发生和发展。启动子CpG岛的高甲基化已被认为是与遗传性缺陷同等重要的、造成抑癌基因在肿瘤中失活的分子生物学机制。虽然有关DNA甲基化肿瘤特异性异化谱式信息仍极有限，但其在肿瘤临床诊断和预后中的巨大潜力已开始得到重视。现结合我们近3年的工作和该领域的最新进展，对DNA甲基化作为肿瘤临床诊断标志物的应用前景进行评估。     

DNA methylation detection methods used in colorectal cancer

Colorectal cancer (CRC) remains a major contributor to the number of cancer-related deaths that occur annually worldwide. With the development of molecular biology methods, an increasing number of molecular biomarkers have been identified and investigated. CRC is believed to result from an accumulation of epigenetic changes, and detecting aberrant DNA methylation patterns is useful for both the early diagnosis and prognosis of CRC. Numerous studies are focusing on the development of DNA methylation detection methods or DNA methylation panels. Thus, this review will discuss the commonly used techniques and technologies to evaluate DNA methylation, their merits and deficiencies as well as the prospects for new methods.     

Tumour budding is a novel marker in breast cancer: the clinical application and future prospects

Breast cancer (BC) is a group of markedly heterogeneous tumours. There are many subtypes with different biological behaviours and clinicopathological characteristics, leading to significantly different prognosis. Despite significant advances in the treatment of BC, early metastatic is a critical factor for poor prognosis in BC patients. Tumour budding (TB) is considered as the first step process of tumour metastasis and is related to the epithelial–mesenchymal transition (EMT). TB has been observed in a variety of cancers, such as colorectal and gastric cancer, and had been considered as a distinct clinicopathological characteristics for early metastasis. However, TB evaluation standards and clinical application are not uniform in BC, as well as its molecular mechanism is not fully understood. Here, we reviewed the interpretation criteria, mechanism, clinicopathological characteristics and clinical application prospects of TB in BC.

Key messages

• Currently, tumour budding is a poor prognosis for various solid tumours, also in breast cancer.
• Tumour budding is based on epithelial-mesenchymal transition and tumour microenvironment factors and is presumed to be an early step in the metastatic process.
• Breast cancer tumour budding still needs multi-centre experiments. We summarize the current research on breast cancer tumour budding, analyse the method of discriminating breast cancer tumour budding and explore the prognostic role and mechanism in breast cancer.

     

抑癌基因CST6及其异常甲基化后在肿瘤发生中的意义

人类半胱氨酸蛋白酶抑制剂基因（cystatinE／MorCST6），又称胱抑C，最初是从转移性乳腺癌细胞中分离出来的一种具有抑制半胱氨酸蛋白酶作用的新基因。有研究发现CST6基因在浸润性乳腺癌、宫颈癌、转移性前列腺癌以及神经胶质脑瘤中表达均有下调，具有抑癌基因的潜能，并且还发现造成该基因表达下调的原因除了基因突变、基因缺失以外，表观遗传修饰的作用更为普遍，而且后者导致的基因沉默可以通过药物逆转。现今有一些关于CST6与癌症发生发展的研究取得了一定的成果。本文综述了CST6基因的功能研究以及其异常甲基化与癌症发生发展关系的研究进展，有望为揭示肿瘤的发生机制提供新的思路，为肿瘤的预防、诊断、治疗提供新的靶点。     

Screening a Prognosis-Related Target Gene in Patients with HER-2-Positive Breast Cancer by Bioinformatics Analysis

ObjectiveThe objective of the present study was to determine a target gene and explore the molecular mechanisms involved in the pathogenesis of HER-2-positive breast cancer.MethodsThree RNA expression profiles obtained from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) were used to identify differentially expressed genes (DEGs) using the R software. A protein-protein interaction network was then constructed, and hub genes were determined. Subsequently, the relationship between clinical parameters and hub genes was examined to screen for target genes. Next, DNA methylation and genomic alterations of the target gene were evaluated. To further explore potential molecular mechanisms, a functional enrichment analysis of genes coexpressed with the target gene was performed.ResultsThe differential expression analysis revealed 217 DEGs in HER-2-positive breast cancer samples compared to normal breast tissues. RRM2 was the only hub gene closely associated with lymphatic metastasis and the patients'' prognosis. Additionally, RRM2 was found to be consistently amplified and negatively associated with the level of methylation. Functional enrichment analysis showed that the coexpressed genes were mainly involved in cell cycle regulation.ConclusionsRRM2 was identified as a target gene associated with the initiation, progression, and prognosis of HER-2-positive breast cancer, which may be considered as a new biomarker and therapeutic target.     

白细胞介素6对卵巢癌恶性演进的影响

现代肿瘤学认为,肿瘤相关性炎症是肿瘤微环境形成的显著特点之一。卵巢癌的发生和发展与微环境中的炎症因子的影响密不可分,白细胞介素6(interleukin 6,IL-6)就是调节肿瘤细胞生长的一种重要的促炎因子。研究发现,在卵巢癌患者中可检测到IL-6及其受体异常高表达,且IL-6升高与临床预后不良密切相关,IL-6对卵巢癌恶性演进的作用机制成为肿瘤微环境领域的研究热点。我们结合课题组近年来的研究成果,主要从IL-6与卵巢癌的增殖、侵袭和转移、血液系统的紊乱、耐药性,IL-6靶向治疗卵巢癌的研究现状和应用前景几方面进行综述。     

Differential DNA methylation status between breast carcinomatous and normal tissues

Breast cancer has been considered to be a multifactorial disease with a wide array of well-characterized gene mutations and chromosomal abnormalities. However, it is becoming evident that the onset or development of breast cancer also depends on epigenetic factors, although the mechanisms have not been fully elucidated. We performed a genome-wide analysis of DNA methylation of breast carcinomatous tissues and paired normal tissues to examine the differences in methylation between them. Methylation-specific polymerase chain reaction (MSP) was used to validate the hypermethylated genes screened out by DNA methylation microarray. We found that hypomethylation and hypermethylation occurred in 2753 and 1795 genes, respectively, in breast carcinomatous tissues. Meanwhile, gene ontology analysis and ingenuity pathway analysis revealed the function and pathway of several genes whose methylation status was altered in breast carcinomatous tissues. In addition, we investigated the promoter methylation status of four genes in breast carcinomatous tissue and paired normal tissues (n = 30) by MSP. Promoter hypermethylation of CRABP1, HOXB13, IFNGR2, and PIK3C3 was found in 37% (11/30), 23% (7/30), 17% (5/30), and 2% (2/30) of the carcinomas, respectively. Mutation of these four important genes was critical to many types of cancer. Our results suggest that DNA methylation mechanisms may be involved in regulating the occurrence and development of breast cancer.     

抑癌基因ECRG4的功能以及其异常甲基化与癌症关系的研究进展

人类食管癌相关基因（ECRG4）是从人类食管上皮细胞内分离出来具有抑癌潜能的新基因,该基因在包括食管癌、乳腺癌,食管上皮鳞状细胞癌,前列腺癌,结直肠癌以及神经胶质细胞瘤等疾病中都有明显的下调。造成该基因表达下调的原因除了基因突变、基因缺失外,表观遗传修饰的作用更为普遍,而且后者导致的基因沉默可以通过药物逆转。本文综述了ECRG4基因的功能研究及其异常甲基化与癌症发生发展关系的研究进展,有望为揭示肿瘤的发生机制提供新的思路,为肿瘤的预防、诊断、治疗提供新的靶点。     

胃癌中甲基化的作用及相关预后标志物研究进展

胃癌已经成为严重威胁人类健康的疾病之一,胃癌的发生与多个基因的异常表达密切相关。抑癌基因启动子高甲基化可使其表达失活,是导致胃癌发生的重要原因之一。随着分子生物学技术的发展,越来越多的肿瘤生物标志物被发现,可以作为临床上早期诊断及预后不良的依据。该文对胃癌发生中启动子甲基化的作用以及潜在甲基化预后标志物的研究进展做了简要的综述,以期能在胃癌发生机制的研究和寻找有效预后生物标志物方面提供相关的信息和思路。     

人黑素瘤药物研究进展

黑素瘤患者死亡率较高。其治疗方法除了传统的手术切除和放射治疗外,化疗一度成为主要的治疗手段。近年来,随着人们对黑素瘤发生发展分子机制的深入研究,基于靶向治疗、生物免疫治疗的方法和药物不断涌现。目前,除了已经在临床治疗中使用的药物外,一些正在进行临床研究的待批准药物和正进行基础研究的潜在药物也表现出良好的应用前景。本文就目前治疗黑素瘤的代表性药物及潜在药物的分子机制及治疗效果作一综述。