MiRNA在结直肠癌干细胞信号通路中的作用

MiRNA是一类内源性非编码的单链小RNA,可以通过调控结直肠癌干细胞(colorectal cancer stem cell,CCSC)等参与结直肠癌(colorectal cancer,CRC)发生发展的各种过程。CCSC被认为是导致CRC发生发展、转移复发以及耐药性的主要原因,mi RNA在CCSC中差异表达,并且可在CRC组织和不同体液中保持一定的特异性和稳定性,因而mi RNA可作为CRC临床早期检测诊断、疗效预测及个体化治疗的新型生物标志物。     

MicroRNAs作为结直肠癌潜在标记物的研究进展

微小RNA(miRNAs)是一种非编码的内源性RNA分子,miRNAs 的异常表达与疾病,尤其与恶性肿瘤的发生、发展存在密切的关系。研究证明,miRNAs可以作为结直肠癌(colorectal cancer,CRC)早期诊断、治疗、预后的新的分子生物学标志物,同时,miRNAs可作为体内CRC治疗的靶点。该文旨在对与CRC相关的miRNAs的表达、功能、作用机制、靶基因等及其在临床应用前景等方面作一综述。     

血液标志物用于结直肠癌早期筛查的研究进展

结直肠癌(colorectal cancer,CRC)是常见的消化道肿瘤,也是世界性疾病。其高发病率和死亡率严重威胁着人类的生命健康。目前,尚缺乏有效的早期筛查方法,以至于CRC患者的手术切除率和生存率不高。近年来关于CRC的早期筛查的研究主要集中在血液中的大分子物质,如DNA、RNA及蛋白质。本文通过将血液中可能成为肿瘤标志物的大分子物质的最新研究做一综述,以期在血液中寻找出能CRC早期筛查的指标。     

结直肠癌中5′tiRNA-Val-CAC对增殖的影响及病理意义

目的 探讨5′tiRNA-Val-CAC在结直肠癌(CRC)中的表达、临床病理意义及其对CRC细胞生长与增殖的影响。方法 分析转运RNA衍生的小RNA(TDSR)表达谱,并通过实时荧光定量聚合酶链反应(qRT-PCR)检测5′tiRNA-Val-CAC表达水平。采用RNA原位杂交技术(RISH)检测82例CRC患者CRC组织及癌旁正常组织中5′tiRNA-Val-CAC阳性表达情况,并分析5′tiRNA-Val-CAC阳性表达与患者临床病理特征的相关性。通过CCK-8实验和细胞克隆平板实验检测5′tiRNA-Val-CAC对CRC细胞生长和增殖的影响。结果 qRT-PCR结果显示,CRC组织中5′tiRNA-Val-CAC表达水平高于癌旁正常组织,差异有统计学意义(t=9.111,P=0.012); CRC细胞系SW620、HCT116中5′tiRNA-Val-CAC表达水平高于正常人肠上皮细胞(HIEC),差异有统计学意义(t=11.475、7.158,P=0.008、0.019)。RISH实验结果显示,CRC组织中5′tiRNA-Val-CAC阳性表达率为82.93%(68/82)...     

长链非编码RNA在结直肠癌中的研究进展

结直肠癌(CRC)是全球第三大恶性肿瘤。长非编码RNA(lncRNA)是一种长度大于200个核苷酸的不编码蛋白质的RNA。各种疾病中lncRNA的异常表达通过不同方式参与其增殖、凋亡、转移和分化等。在CRC也发现了lncRNA的异常表达。本文阐述了不同lncRNA在CRC中的作用,以及它们临床应用的潜在价值。     

微小RNA在结直肠癌中的研究进展

结直肠癌(colorectal carcinoma,CRC)是消化系统最常见的恶性肿瘤之一,随着中国生活条件和饮食习惯的改变,CRC发病率呈明显上升趋势。因此,对CRC发生、发展的机制以及早期诊断标志物的研究是目前CRC研究的重点。自研究者在秀丽隐杆线虫(C.elegans)中发现了第1个定时调控胚胎后期     

结直肠癌中miRNA功能及临床价值研究进展

结直肠癌(CRC)是十分常见的消化道恶性肿瘤,其致病机制十分复杂。微小RNA(miRNA)是分布十分广泛的非编码RNA,在包括CRC在内的多种恶性肿瘤的致病过程中发挥着重要的调控作用。作为无创的生物学指标,大量的研究数据显示特异性miRNA用于CRC的临床诊断及预后评估具有良好的应用价值。基于细胞或动物模型的研究也显示靶向特定miRNA的分子治疗方法用于CRC具有较好的疗效,但距离临床实际应用仍有许多困难需要克服。     

外周血游离线粒体DNA定量检测在结直肠癌患者中的表达及意义

目的评价外周血游离线粒体DNA(circulating cell free mitochondrial DNA, CCF mtDNA)在结直肠癌(colorectal cancer, CRC)患者组织中的表达及其临床意义。方法收集102例CRC患者的癌组织及癌旁组织标本、30例原发性CRC患者及体检健康者血浆标本,实时荧光定量PCR检测各组CCF mtDNA的表达水平,并分析CCF mtDNA含量与CRC患者临床病理参数的关系。ROC曲线分析其作为CRC筛查标志物的效能。结果 CRC患者癌组织中的CCF mtDNA含量(85.94±4.54)明显低于癌旁组织(183.10±7.59),差异有统计学意义(t=11.04,P0.05)。低分化癌组织中的CCF mtDNA含量(57.75±5.26)明显低于中分化(92.64±5.68)及高分化(110.00±14.95)癌组织,差异有统计学意义(F=8.42,P0.05)。CCF mtDNA含量高低与CRC患者的预后无关(χ~2=0.261,P=0.610)。CCF mtDNA筛查CRC的AUC~(ROC)为0.921,敏感性为0.833,特异性为0.933。结论 CCF mtDNA含量在癌组织中下降,但与预后无关,可能作为CRC的筛查标志物。     

microRNA在结直肠癌诊断、治疗及预后中的研究进展

结直肠癌(colorectal cancer,CRC)由于其高患病率和死亡率成为世界性的公共卫生问题。研究发现,微小RNA(microRNA,miRNA)在CRC发生、发展中起着重要的作用,与CRC的诊断、分期、进展和预后密切相关,为CRC的早期发现和治疗起到一定的指导作用。该文就miRNA的产生及功能、检测技术及其在CRC中的临床应用价值作一综述。     

粪便SDC2基因甲基化检测在结直肠癌筛查中的应用价值

目的 探讨粪便硫酸类肝素蛋白多糖2(SDC2)基因甲基化检测在结直肠癌(CRC)筛查中的临床应用价值。方法 通过荧光聚合酶链反应(PCR)法检测在该院胃肠外科或消化内科就诊的96例患者粪便中SDC2基因甲基化情况,并收集其6种血清肿瘤标志物[血清癌胚抗原(CEA)、糖类抗原(CA)19-9、CA125、铁蛋白(SF)、细胞角蛋白19片段(CYFRA-21)、胃泌素释放肽前体(ProGRP)]的联合检测结果及肠镜、病理检查结果,以肠镜及病理检查结果为“金标准”分析比较粪便SDC2基因甲基化与6种血清肿瘤标志物检测对CRC的诊断效能。同时分析粪便SDC2基因甲基化与TNM分期及癌变部位等临床病理特征的关系。结果 根据肠镜或病理检查结果,将96例就诊者分为CRC组(32例)和对照组(64例),CRC组中粪便SDC2基因甲基化检测阳性率为84%(27/32),6种血清肿瘤标志物联合检测阳性率为44%(14/32);对照组中粪便SDC2基因甲基化检测阳性率为3%(2/64),6种血清肿瘤标志物联合检测阳性率为20%(13/64)。粪便SDC2基因甲基化诊断CRC的特异度(97%)、灵敏度(84%...     

Role of gut microbiome in regulating the effectiveness of metformin in reducing colorectal cancer in type 2 diabetes

The prevalence of colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM) is increasing globally. It is rarely noticed that the incidence of CRC is higher in patients with T2DM. What needs to be mentioned is that metformin, a commonly used clinical drug for T2DM, attracts scholars’ attention because of its benefits in lowering the risk of developing CRC. Hence, we try to find the common grounds of initiation of T2DM and CRC and the reason why metformin reduces the risk of CRC in patients with T2DM. We noticed consistent changes of gut microbiota, such as elevated Bacteroides, Prevotella and Bifidobacterium and depressed Firmicutes and Lactobacillus. Furthermore, many studies in recent years have proved that the efficacy of metformin, such as improving blood glucose, depends on the gut microbiota. Coincidentally, the progression of CRC is inseparable from the contributions of gut microbiota. Therefore, we first proposed the concept of the metformin-gut microbiota–CRC (in T2DM) axis to explain the effect of metformin in reducing CRC in patients with T2DM. In this review, we elaborated the new concept and its potential clinical application value.     

Expression of Lgr5, a marker of intestinal stem cells,in colorectal cancer and its clinicopathological significance

Cancer stem cells (CSCs) have been the focus of intense investigations in cancer research although the cellular origin of CSCs has not been clearly determined. Lgr5 is a regulated target of Wnt/β-catenin signaling, which was first identified as a marker of intestinal stem cells. However, the expression of Lgr5 in human colorectal cancer (CRC) and its clinical clinicopathological significance in CRC patients as well as its correlation with Wnt/β-catenin pathway are not fully explored. Localization and expression of Lgr5 in CRC tissues was performed by immunohistochemical staining. The correlation between its expression levels and clinicopathological features as well as clinical outcomes of patients was analysed. The quantitative expression levels of Lgr5 in various CRC cell lines were determined using real-time RT-PCR. The relationship between Lgr5 expression and Wnt/β-catenin pathway in CRC was also investigated. Obviously elevated expression of Lgr5 was observed in CRC tissues, compared to the paired nontumor tissues. mRNA expression levels of Lgr5 was positively correlated with the expression of β-catenin in CRC tissues. The expression of Lgr5 was various in different CRC cell lines. Low and high expression levels of Lgr5 were significantly correlated with clinicopathological features such as TNM stage, lymph node metastasis and vascular invasion of CRC patients. More importantly, Lgr5 expression in CRC tissues was also associated with tumor angiogenesis as well as clinical outcomes. Taken together, these results suggest that elevated Lgr5 expression might contribute to the development and progression of CRC, and it could also be used a potential unfavorable prognostic biomarker for CRC. A better understanding of molecule mechanisms and the relevance of potential value for Lgr5 in the progression of CRC will help to identify a novel therapeutic strategy for CRC patients.     

A Collaborative Survey of Nurse Practitioner Colorectal Cancer Screening Practice

Colorectal cancer (CRC) is the second leading cause of cancer death in men and women in the United States. The opportunity for nurse practitioners (NPs) to initiate preventive measures to guide early detection of CRC is great given its slow progression. We present a collaborative project between a state NP association and colleagues from the Medical Affairs Division of a pharmaceutical company to develop an electronic survey to assess NP knowledge, beliefs, and practice patterns for CRC screening. Survey data identified that NP knowledge of CRC screening guidelines is variable and may contribute to low screening rates.     

组蛋白去乙酰化酶5下调SIX1的表达以抑制结直肠癌细胞增殖的研究

目的探讨组蛋白去乙酰化酶5(HDAC5)在结直肠癌组织中的表达情况以及在结直肠癌细胞系中的机制。方法采用免疫组织化学技术检测HDAC5在结直肠癌组织中的表达情况,分析HDAC5表达量与患者生存预后的关系。在细胞水平敲除HDAC5后,观察细胞的增殖、迁移能力以及凋亡功能的变化。结果 HDAC5在结直肠癌组织中的阳性表达与生存预后较差显著相关。在肿瘤细胞系中,HDAC5通过调控SIX1影响细胞的增殖。结论 HDAC5在结直肠癌组织表达有差异,与结直肠癌生存预后相关,并可通过调控SIX1的表达影响细胞的增殖。     

CXCL2在结直肠癌中的表达及临床意义

目的检测CXCL2蛋白在结直肠癌中的表达情况,探讨其临床研究意义。方法利用Oncomine芯片数据库分析6个独立的研究中结直肠癌CXCL2mRNA的表达数据。采用组织芯片(TMA)免疫组化染色检测结直肠癌CXCL2蛋白的表达情况,并用统计学分析其与临床病理特征和预后的相关性。结果 CXCL2在结直肠癌较其癌旁组织中高表达;31.31%的结直肠癌细胞质CXCL2高表达,与肿瘤部位(P=0.022)、原发肿瘤的浸润程度(P=0.005)及淋巴结转移(P=0.017)显著相关;Kaplan-Meier和Cox回归分析表明,CXCL2高表达(P0.001)是结直肠癌预后不良的一项独立预测因素。结论 CXCL2高表达可能与结直肠癌的侵袭和转移有关,可作为结直肠癌的预后指标和治疗的潜在靶点。     

常规临床检验指标与结直肠癌临床病理参数的关联分析及诊断预测价值

目的 探讨常规临床检验指标(血细胞炎性指标和血清肿瘤标志物)与结直肠癌(CRC)患者临床病理参数的相关性,并建立诊断预测CRC的列线图.方法 回顾性分析370例初诊CRC患者临床资料,统计分析常规临床检验指标与CRC患者临床病理参数的关系及其诊断效能,通过多因素Logistic回归分析确定CRC的独立危险因素,建立用于...     

Overexpression of lncRNA AFAP1-AS1 correlates with poor prognosis and promotes tumorigenesis in colorectal cancer

Accumulating evidence has shown that long non-coding RNAs (lncRNAs) are emerging as key molecules in human malignancies. The lncRNA actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) was recently found deregulated in several cancers. However, its expression pattern, clinical performance and functional roles in colorectal cancer (CRC) had not been addressed. In this study, we found that AFAP1-AS1 was aberrantly over-expressed in CRC tissues and closely correlated with tumor size, TNM stage and distant metastasis. Kaplan-Meier analysis indicated that patients with high level of AFAP1-AS1 expression had poorer overall survival (OS) and disease-free survival (DFS). Univariate and multivariable Cox regression analyses further identified that up-regulated AFAP1-AS1 might act as an independent prognostic factor for CRC patients. Moreover, AFAP1-AS1 depletion resulted in the inhibition of CRC cell proliferation and colony formation. In addition, AFAP1-AS1 knockdown induced G0/G1 cell cycle arrest in CRC cells. Taken together, our findings indicate that AFAP1-AS1 is significantly up-regulated in CRC, which may act as an oncogene and correlate with tumor malignant progression and poor prognosis of CRC. This study may shed a new light on better understanding the pathogenesis of CRC. Moreover, AFAP1-AS1 also may be a promising diagnostic and therapeutic target for this deadly disease.     

Fecal oncomarkers in the diagnostics of colorectal cancer

Colorectal cancer (CRC) presents one of the central problems in modern medicine. In approximately every third patient, colon cancer is revealed at stage IV, which determines the patient's outcome. Early diagnosis is possible only at the pre-clinical stage. To find a cheap and non-invasive diagnostic method which would determine indications to endoscopy is an important task of modern medicine. The authors studied what benefits in CRC diagnostics were provided by fecal calprotectin test and different methods for detection of occult blood in feces as well as combinations of these. The study found that calprotectin test and immunochemical test were more sensitive than hemocult-test for CRC diagnostics (p < 0.05). Immunochemical occult blood test proved to be more sensitive for the detection of polyps or any kind of colon dysplasia (p < 0.05). Hence, despite its relatively high cost, immunochemical occult blood test may be recommended as a non-invasive colorectal cancer marker in individuals with moderate risk, while fetal calprotectin test, being cheap and easily repeatable, may be used for screening only in patients with a high risk of CRC development. Combined application of tests for occult blood and calprotectin in feces makes it possible to increase the sensitivity of the method up to 97.2%, its specificity up to 93.3%, and its effectiveness up to 95.6% in the detection of CRC.     

结直肠癌患者外周血CEA-mRNA表达的研究

目的 检测结直肠癌患者外周血中的循环肿瘤细胞癌胚抗原（CEA）mRNA的表达,并分析其临床价值。方法 40例有明确临床肿瘤病灶存在的结肠癌患者,20例结肠息肉患者和40例健康志愿者,分别以逆转录PCR（RT-PCR）检测其外周血中CEA mRNA的表达。结果 40例结肠癌患者外周血中CEA mRNA表达的阳性率为45.0%（18/40）,而健康对照组均为阴性,两者比较有显著性差异（P〈0.001）;20例结肠息肉患者中CEA mRNA表达阳性率为10%（2/20）;CEA mRNA阳性表达率与肿瘤分期相关,而与肿瘤细胞分化程度并不相关。结论 结直肠癌患者外周血中CEA mRNA的表达的检测对肿瘤的分期、决定治疗手段、判断疗效和预后有着重要的临床价值。