Circulating microRNA's as a diagnostic tool for hepatocellular carcinoma in a hyper endemic HIV setting, KwaZulu-Natal, South Africa: a case control study protocol focusing on viral etiology.

Circulating microRNA's as a diagnostic tool for hepatocellular carcinoma in a hyper endemic HIV setting, KwaZulu-Natal, South Africa: a case control study protocol focusing on viral etiology.
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DOI:
10.1186/s12885-017-3915-z
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发表时间:
2017-12-28
期刊:
影响因子:
3.8
通讯作者:
Winkler CA
Winkler CA
中科院分区:
医学2区
文献类型:
--
作者:
Sartorius K;Sartorius B;Kramvis A;Singh E;Turchinovich A;Burwinkel B;Madiba T;Winkler CA

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广泛的研究调查了细胞外microRNAs (miRNAs)在肝细胞癌(HCC)中的诊断能力。由于流行的病毒感染水平(HBV/HIV)、老龄化和生活方式的改变,预计撒哈拉以南非洲(SSA)的HCC将增加。这一独特的病因学背景为在南非的一项前瞻性研究中研究潜在的新型循环mirna作为HCC的生物标志物提供了机会。这项研究将从位于夸祖鲁-纳塔尔省德班和彼得马里茨堡的两家南非癌症医院招募HCC患者。这些病例将包括HBV单一感染和HBV/HIV合并感染的HCC病例。对照组将由两(2)个年龄和性别匹配的健康人群组成,每个HCC病例从德班实验室随机选择。对照组将排除有任何慢性肝病证据的患者。将采用标准化的报告方法来检测、量化和规范HCC患者及其对照组血清中循环mirna的水平。逆转录定量聚合酶链反应(RT-qPCR)将用于细胞外mirna的定量。病例/对照状态下相关miRNA浓度的差异将使用Wilcoxon秩和(Mann-Whitney U)检验进行评估。将采用多重检验调整(Bonferroni校正)、受试者工作曲线(ROC)和最佳断点分析来确定HCC病例及其对照组miRNA水平分化的潜在阈值。尽管关于循环mirna作为生物标志物的作用的文献越来越多,但这一有前途的领域仍然是“正在进行的工作”。HCC中HBV感染的病因及其在miRNA失调中的作用已被充分了解,然而,HIV感染的介导作用尚不清楚。预计未来十年,包括南非在内的SSA地区的HCC发病率将显著增加。因此,多种因素的结合为鉴定候选循环mirna作为HBV/HIV感染HCC的潜在生物标志物提供了独特的机会。本文的在线版本(10.1186/s12885-017-3915-z)包含补充内容,仅供授权用户使用。
A wide range of studies has investigated the diagnostic proficiency of extracellular microRNAs (miRNAs) in hepatocellular cancer (HCC). HCC is expected to increase in Sub-Saharan Africa (SSA), due to endemic levels of viral infection (HBV/HIV), ageing and changing lifestyles. This unique aetiological background provides an opportunity for investigating potentially novel circulating miRNAs as biomarkers for HCC in a prospective study in South Africa. This study will recruit HCC patients from two South African cancer hospitals, situated in Durban and Pietermaritzburg in the province of KwaZulu-Natal. These cases will include both HBV mono-infected and HBV/HIV co-infected HCC cases. The control group will consist of two (2) age and sex-matched healthy population controls per HCC case randomly selected from a Durban based laboratory. The controls will exclude patients if they have any evidence of chronic liver disease. A standardised reporting approach will be adopted to detect, quantify and normalize the level of circulating miRNAs in the blood sera of HCC cases and their controls. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) will be employed to quantity extracellular miRNAs. Differences in concentration of relevant miRNA by case/control status will be assessed using the Wilcoxon rank-sum (Mann-Whitney U) test. Adjustment for multiple testing (Bonferroni correction), receiver operating curves (ROC) and optimal breakpoint analyses will be employed to identify potential thresholds for the differentiation of miRNA levels of HCC cases and their controls. Although there is a growing base of literature regarding the role of circulating miRNAs as biomarkers, this promising field remains a ‘work in progress’. The aetiology of HBV infection in HCC is well understood, as well as it’s role in miRNA deregulation, however, the mediating role of HIV infection is unknown. HCC incidence in SSA, including South Africa, is expected to increase significantly in the next decade. A combination of factors, therefore, offers a unique opportunity to identify candidate circulating miRNAs as potential biomarkers for HBV/HIV infected HCC. The online version of this article (10.1186/s12885-017-3915-z) contains supplementary material, which is available to authorized users.
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