Serum Metabolomics and Liver Cancer Title: Serum Metabolomics and Liver Cancer Translational Relevance Serum Metabolomics and Liver Cancer

1 Purpose: Metabolomics depicts metabolic changes in biological systems using a 2 multiparametric analysis technique. This study assessed the metabolomic profiles of 3 serum, obtained by proton NMR spectroscopy, from cirrhotic patients with and without 4 hepatocellular carcinoma (HCC). Experimental Design: The study included 154 5 consecutive patients with compensated biopsy-proven alcoholic cirrhosis. Among these, 6 93 had cirrhosis without HCC, 28 had biopsy-proven HCC within the Milan criteria and 7 were eligible for curative treatment ('small' HCC) and 33 had HCC outside the Milan 8 criteria ('large' HCC). Proton spectra were acquired at 500 MHz. An orthogonal partial 9 latent structure (OPLS) analysis model was built to discriminate large HCC spectra from 10 cirrhotic spectra. Small HCC spectra were secondarily projected using previously built 11 OPLS discriminant components. Results: The OPLS model showed discrimination 12 between cirrhotic and large HCC spectra. Metabolites that significantly increased with 13 large HCC were, glutamate, acetate and N-acetyl glycoproteins, whereas metabolites that 14 correlated with cirrhosis were lipids and glutamine. Projection of small HCC samples 15 into the OPLS model showed a heterogeneous distribution between large HCC and 16 cirrhotic samples. Small HCC patients with metabolomic profile similar to those of large 17 HCC group had higher incidences of recurrence or death during follow-up. Conclusions: 18 Serum NMR-based metabolomics identified metabolic fingerprints that could be specific 19 to large HCC in cirrhotic livers. From a metabolomic standpoint, some patients with 20 small HCC, who are eligible for curative treatments, seem to behave as patients with 21 advanced cancerous disease. It would be useful to further prospectively investigate 22 these patients to define a subgroup with a worse prognosis. 23 24 Research. on April 19, 2017. © 2012 American Association for Cancer clincancerres.aacrjournals.org Downloaded from Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on November 7, 2012; DOI: 10.1158/1078-0432.CCR-12-1099