Characterization of Urinary Biomarkers of Hepatocellular Carcinoma Using Magnetic Resonance Spectroscopy in a Nigerian Population

Abstract

Hepatocellular carcinoma (HCC) is the commonest primary hepatic malignancy worldwide. Current serum diagnostic biomarkers, such as alpha-fetoprotein, are expensive and insensitive in early tumor diagnosis. Urinary biomarkers differentiating HCC from chronic liver disease would be practical and widely applicable. Using an 11.7T nuclear magnetic resonance system, urine was analyzed from three well-matched subject groups, collected at Jos University Teaching Hospital (JUTH), Nigeria. Multivariate factor analyses were performed using principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). All patients were of Nigerian descent: 18 hepatitis B surface antigen (HBsAg)-positive patients with HCC, 10 HBsAg positive patients with cirrhosis, and 15 HBsAg negative healthy Nigerian controls. HCC patients were distinguished from healthy controls, and from the cirrhosis cohort, with sensitivity/specificity of 100%/93% and 89.5%/88.9%, respectively. Metabolites that most strongly contributed to the multivariate models were creatinine, carnitine, creatine and acetone. Urinary (1)H MRS with multivariate statistical analysis was able to differentiate patients with HCC from normal subjects and patients with cirrhosis. Creatinine, carnitine, creatine and acetone were identified as the most influential metabolites. These findings have identified candidate urinary HCC biomarkers which have potential to be developed as simple urinary screening tests for the clinic.

Identification of Serum Proton NMR Metabolomic Fingerprints Associated with Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis

“…The usual major limitation encountered in a translational metabolomic approach to liver diseases is methodologic bias when selecting patients, thus limiting the confidence that can be drawn from conclusions (8,9,16). We attempted to avoid these pitfalls by constructing well-defined subgroups of patients according to their stage of underlying liver disease and HCC status.…”

Magnetic Resonance Spectroscopy: Principles and Techniques: Lessons for Clinicians

“…Shariff and colleagues, in two 1 H NMR spectroscopy studies, have investigated the urine of Nigerian and Egyptian populations, comparing urine samples from patients with cirrhosis and those with hepatocellular carcinoma. 41,42 Multivariate analysis uncovered a clear distinction in urinary metabolites between the two cohorts. These included reduced urinary creatinine, glycine, hippurate, trimethylamine-N-oxide, and citrate while urinary carnitine, creatine and acetone were raised.…”

Acetylcarnitine Is a Candidate Diagnostic and Prognostic Biomarker of Hepatocellular Carcinoma

“…Current metabolomics studies on hepatocellular carcinoma are mainly focused on identifying significant metabolites in serum/ urine samples with the aim of revealing systemic metabolic changes caused by hepatocellular carcinoma and finding potential biomarkers with clinical application (15)(16)(17)(18)(19)(20)(21)(22). There has been limited analysis of the effects of hepatocellular carcinoma on liver metabolism (23,24).…”