The utility of biomarkers in hepatocellular carcinoma: review of urine-based 1H-NMR studies – what the clinician needs to know

Caroline R Cartlidge,1 M R Abellona U,2 Alzhraa M A Alkhatib,2 Simon D Taylor-Robinson1 1Department of Surgery and Cancer, Liver Unit, Division of Digestive Health, 2Department of Surgery and Cancer, Division of Computational and Systems Medicine, Faculty of Medicine, Imperial College London, London, UK Abstract: Hepatocellular carcinoma (HCC) is the fifth most common malignancy, the third most common cause of cancer death, and the most common primary liver cancer. Overall, there is a need for more reliable biomarkers for HCC, as those currently available lack sensitivity and specificity. For example, the current gold-standard biomarker, serum alpha-fetoprotein, has a sensitivity of roughly only 70%. Cancer cells have different characteristic metabolic signatures in biofluids, compared to healthy cells; therefore, metabolite analysis in blood or urine should lead to the detection of suitable candidates for the detection of HCC. With the advent of metabonomics, this has increased the potential for new biomarker discovery. In this article, we look at approaches used to identify biomarkers of HCC using proton nuclear magnetic resonance (1H-NMR) spectroscopy of urine samples. The various multivariate statistical analysis techniques used are explained, and the process of biomarker identification is discussed, with a view to simplifying the knowledge base for the average clinician. Keywords: hepatocellular carcinoma, biomarkers, metabonomics, urine, proton nuclear magnetic resonance spectroscopy, 1H-NMR&nbsp