Identification of serum proton NMR metabolomic fingerprints associated with hepatocellular carcinoma in patients with alcoholic cirrhosis

P. Nahon , R. Amathieu , M.N. Triba , N. Bouchemal , J.-C. Nault (1) , M. Ziol , O. Seror , G. Dhonneur , J.-C. Trinchet , M. Beaugrand , L. Le Moyec (2)

1 UP13 - Université Paris 13
2 UBIAE - Unité de biologie intégrative des adaptations à l'exercice

Purpose Metabolomics depicts metabolic changes in biologic systems using a multiparametric analysis technique. This study assessed the metabolomic profiles of serum, obtained by proton nuclear magnetic resonance (NMR) spectroscopy, from cirrhotic patients with and without hepatocellular carcinoma (HCC). Experimental Design The study included 154 consecutive patients with compensated biopsy-proven alcoholic cirrhosis. Among these, 93 had cirrhosis without HCC, 28 had biopsy-proven HCC within the Milan criteria and were eligible for curative treatment (small HCC), and 33 had HCC outside the Milan criteria (large HCC). Proton spectra were acquired at 500 MHz. An orthogonal partial latent structure [orthogonal projection to latent structure (OPLS)] analysis model was built to discriminate large HCC spectra from cirrhotic spectra. Small HCC spectra were secondarily projected using previously built OPLS discriminant components. Results The OPLS model showed discrimination between cirrhotic and large HCC spectra. Metabolites that significantly increased with large HCC were glutamate, acetate, and N-acetyl glycoproteins, whereas metabolites that correlated with cirrhosis were lipids and glutamine. Projection of small HCC samples into the OPLS model showed a heterogeneous distribution between large HCC and cirrhotic samples. Small HCC patients with metabolomic profile similar to those of large HCC group had higher incidences of recurrence or death during follow-up. Conclusions Serum NMR-based metabolomics identified metabolic fingerprints that could be specific to large HCC in cirrhotic livers. From a metabolomic standpoint, some patients with small HCC, who are eligible for curative treatments, seem to behave as patients with advanced cancerous disease. It would be useful to further prospectively investigate these patients to define a subgroup with a worse prognosis. ©2012 AACR.

Keywords: Liver Neoplasms; Magnetic Resonance Spectroscopy; Male; Metabolome; Middle Aged; Multivariate Analysis; Principal Component Analysis; Prognosis; ROC Curve; Tumor Markers; Biological; acetic acid; carbene; fatty acid; fatty acid ester; glutamic acid; glutamine; lipid; n acetylglycoprotein; unclassified drug; adult; alcohol liver cirrhosis; article; blood analysis; cancer incidence; cancer mortality; cancer recurrence; cancer staging; Caucasian; cohort analysis; differential diagnosis; follow up; genetic association; genetic engineering; human; lipid blood level; liver biopsy; liver carcinogenesis; liver cell carcinoma; major clinical study; metabolomic fingerprint; metabolomics; orthogonal partial latent structure; priority journal; protein blood level; proton nuclear magnetic resonance; radiofrequency; radiological parameters; serum characteristics; spectroscopy; Aged; Area Under Curve; Carcinoma; Hepatocellular; Female; Humans; Liver Cirrhosis; Alcoholic

Domains: Life Sciences [q-bio]

P. Nahon, R. Amathieu, M.N. Triba, N. Bouchemal, J.-C. Nault, et al.. Identification of serum proton NMR metabolomic fingerprints associated with hepatocellular carcinoma in patients with alcoholic cirrhosis. Clinical Cancer Research, 2012, 18 (24), pp.6714-6722. ⟨10.1158/1078-0432.CCR-12-1099⟩. ⟨hal-02489955⟩