The Plasma and Serum Metabotyping of Hepatocellular Carcinoma in a Nigerian and Egyptian Cohort using Proton Nuclear Magnetic Resonance Spectroscopy

Mohamed I F Shariff; Jin Un Kim; Nimzing G Ladep; Asmaa I Gomaa; Mary M E Crossey; Edith Okeke; Edmund Banwat; Imam Waked; I Jane Cox; Roger Williams; Elaine Holmes; Simon D Taylor-Robinson

doi:10.1016/j.jceh.2017.03.007

The Plasma and Serum Metabotyping of Hepatocellular Carcinoma in a Nigerian and Egyptian Cohort using Proton Nuclear Magnetic Resonance Spectroscopy

J Clin Exp Hepatol. 2017 Jun;7(2):83-92. doi: 10.1016/j.jceh.2017.03.007. Epub 2017 Mar 15.

Authors

Affiliations

¹ Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, St Mary's Campus, South Wharf Road, London W2 1NY, United Kingdom.
² National Liver Institute, Menoufiya University, Shebeen El Kom, Egypt.
³ Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, United Kingdom.
⁴ Department of Medicine, Jos University Teaching Hospital, Plateau State, Nigeria.
⁵ The Foundation for Liver Research, Institute of Hepatology, 69-75 Chenies Mews, London WC1E 6HX, United Kingdom.

Abstract

Background/aims: Previous studies have observed disturbances in the ¹H nuclear magnetic resonance (NMR) blood spectral profiles in malignancy. No study has metabotyped serum or plasma of hepatocellular carcinoma (HCC) patients from two diverse populations. We aimed to delineate the HCC patient metabotype from Nigeria (mostly hepatitis B virus infected) and Egypt (mostly hepatitis C virus infected) to explore lipid and energy metabolite alterations that may be independent of disease aetiology, diet and environment.

Methods: Patients with HCC (53) and cirrhosis (26) and healthy volunteers (19) were recruited from Nigeria and Egypt. Participants provided serum or plasma samples, which were analysed using 600 MHz ¹H NMR spectroscopy with nuclear Overhauser enhancement spectroscopy pulse sequences. Median group spectra comparison and multivariate analysis were performed to identify regions of difference.

Results: Significant differences between HCC patients and healthy volunteers were detected in levels of low density lipoprotein (P = 0.002), very low density lipoprotein (P < 0.001) and lactate (P = 0.03). N-acetylglycoproteins levels in HCC patients were significantly different from both healthy controls and cirrhosis patients (P < 0.001 and 0.001).

Conclusion: Metabotype differences were present, pointing to disturbed lipid metabolism and a switch from glycolysis to alternative energy metabolites with malignancy, which supports the Warburg hypothesis of tumour metabolism.

Keywords: 1-D, One-dimensional; 1H NMR, proton nuclear magnetic resonance; AFP, α-fetoprotein; ALP, Alkaline phosphatase; ALT, Alanine transaminase; CT, Computed Tomography; EDTA, Ethylenediaminetetraacetic acid; ELISA, Enzyme-linked immunosorbent assay; Egypt; FID, Free induction decays; HBV, Hepatitis B virus; HBsAg, Hepatitis B surface antigen; HCC, Hepatocellular carcinoma; HCV, Hepatitis C virus; IDL, Intermediate density lipoprotein; IQR, Interquartile ranges; JUTH, Jos University Teaching Hospital; LDL, Low density lipoprotein; MRI, Magnetic resonance imaging; NOESY, Nuclear Overhauser enhancement spectroscopy; Nigeria; PC, Principal component; PCA, Principal components analysis; PLS-DA, Partial least squared discriminant analysis; PPARα, Peroxisome proliferator-activated receptor α; RD, Relaxation delay; US, Ultrasonography; VLDL, Very low density lipoprotein; WHO, World Health Organisation; hepatocellular carcinoma; ppm, Parts per million; proton nuclear magnetic resonance spectroscopy; serum metabotype; tm, Mixing time.