The online version of this article (https://doi.org/10.1186/s12885-017-3915-z) contains supplementary material, which is available to authorized users.
K. Sartorius and B. Sartorius are joint first authors.
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.
Pritchard CC, Kroh E, Wood B, Arroyo JD, Dougherty KJ, Miyaji MM, Tait JF, Tewari M. Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies. Cancer Prev Res. 2012;5(3):492–7. CrossRef
Etheridge A, Gomes CP, Pereira RW, Galas D, Wang K. The complexity, function, and applications of RNA in circulation. The origin, function and diagnostic potential of extracellular microRNA in human body fluids; 2014. p. 19.
Sun J, Lu H, Wang X, Jin H. MicroRNAs in hepatocellular carcinoma: regulation, function, and clinical implications. Sci World J. 2013;924206. http://doi.org/10.1155/2013/924206.
Piedade D, Azevedo-Pereira JM: MicroRNAs, HIV and HCV: a complex relation towards pathology. Rev Med Virol. 2016;26(3):197–215.
Makarova JA, Shkurnikov MU, Wicklein D, Lange T, Samatov TR, Turchinovich AA, Tonevitsky AG: Intracellular and extracellular microRNA: an update on localization and biological role. Prog Histochem Cytochem. 2016;51(3-4):33–49. doi: 10.1016/j.proghi.2016.06.001. Epub 2016 Jun 25.
Turchinovich A, Samatov T, Tonevitsky A, Burwinkel B. Circulating miRNAs: cell–cell communication function? The origin, function and diagnostic potential of extracellular microRNA in human body fluids; 2014. p. 27.
- 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
C. A. Winkler
- BioMed Central
Neu im Fachgebiet Onkologie
Mail Icon II