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

BMC Cancer

Study Protocol

C. A. Winkler¹  K. Sartorius²  B. Sartorius³  A. Kramvis⁴  B. Burwinkel⁵  A. Turchinovich⁶  E. Singh⁷  T. Madiba⁸ 

[1] Basic Research Laboratory, Centre for Cancer Research, National Cancer Institute, Leidos Biomedical Research, Inc. Frederick Nat. Lab. for Cancer Research, Frederick, MD, USA;Department of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, 4041, Durban, South Africa;Faculty of Commerce, Law and Management, University of the Witwatersrand, Johannesburg, South Africa;UKZN Gastrointestinal Cancer Research Centre (GICRC), Durban, South Africa;Department of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, 4041, Durban, South Africa;UKZN Gastrointestinal Cancer Research Centre (GICRC), Durban, South Africa;Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg, South Africa;Molecular Epidemiology Group, German Cancer Research Centre, Heidelberg, Germany;Molecular Epidemiology Group, German Cancer Research Centre, Heidelberg, Germany;SciBerg e.Kfm, Mannheim, Germany;South African National Cancer Registry, National Health Laboratory Service, Johannesburg, South Africa;UKZN Gastrointestinal Cancer Research Centre (GICRC), Durban, South Africa;

关键词: Hepatocellular carcinoma;    miRNA;    Biomarker;    Diagnosis;    Staging;    HBV;    HIV;   

DOI  :  10.1186/s12885-017-3915-z

 received in 2016-12-06, accepted in 2017-12-14,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundA 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.MethodsThis 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.DiscussionAlthough 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.

【 授权许可】

CC BY   
© The Author(s). 2017