Early Diagnosis of Hepatocellular Carcinoma by MicroRNAs: Shining a Light from the Genome’s “Dark Matter”

Excerpt

Hepatocellular carcinoma (HCC) is the leading cause of death among patients with chronic hepatitis and cirrhosis [1]. Chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the most frequent etiological factors for cirrhosis and accounts for approximately 50 and 25 % of all HCC cases, respectively [2]. Other important risk factors for HCC include alcohol consumption and HIV infection. Both are susceptible to exerting a more rapid progression from cirrhosis to HCC due to a synergistic effect in individuals with HBV and/or HCV infections [3]. Accordingly, 80–90 % of patients with HCC have an established background of chronic hepatitis and cirrhosis [4]; consequently, both conditions should be considered components of the HCC-associated multistep process. In this scenario, only surveillance and early diagnosis will potentially reduce the high mortality rate of HCC. Current surveillance of HCC relies on abdominal ultrasonography. This non-invasive, image-based approach has shown nearly 100 % specificity [1]. Unfortunately, ultrasonography requires the expert assessment of images acquired by state-of-the-art equipment, which may not always be available for large-scale surveillance approaches. Alternatively, blood-based biomarkers, such as HCC-secreted proteins to serum or plasma, are an attractive approach because of their non-invasiveness as well as their reproducible and cost-effective assessments. Alpha-Fetoprotein (AFP), a glycoprotein produced by the fetal liver and yolk sac during pregnancy, is the best example of these types of biomarkers. Although levels of >500 ng/mL are indicative of HCC, this is not the case in the early stages of HCC. Moreover, raised concentrations of AFP have been found in patients with HBV and/or HCV infections. Thus, AFP may not be the best candidate for the early diagnosis of HCC. Recently, another HCC-secreted protein, Dickkopf-1 (DKK1), a member of the Dickkopf family involved in embryonic development, has emerged as a potential biomarker for the early diagnosis of HCC. However, DKK1 has been suggested only as a complement to AFP to enhance the accuracy of the serological diagnoses of HCC [5]. …