Potential conflict of interest: Nothing to report.
Imaging mass spectrometry reveals modified forms of histone H4 as new biomarkers of microvascular invasion in hepatocellular carcinomas
Article first published online: 30 JUL 2013
© 2013 by the American Association for the Study of Liver Diseases
Volume 58, Issue 3, pages 983–994, September 2013
How to Cite
Poté, N., Alexandrov, T., Le Faouder, J., Laouirem, S., Léger, T., Mebarki, M., Belghiti, J., Camadro, J.-M., Bedossa, P. and Paradis, V. (2013), Imaging mass spectrometry reveals modified forms of histone H4 as new biomarkers of microvascular invasion in hepatocellular carcinomas. Hepatology, 58: 983–994. doi: 10.1002/hep.26433
- Issue published online: 29 AUG 2013
- Article first published online: 30 JUL 2013
- Accepted manuscript online: 2 APR 2013 04:31AM EST
- Manuscript Accepted: 26 MAR 2013
- Manuscript Received: 25 JAN 2013
- “Fondation pour la Recherche Médicale,” the “Société Française de Pathologie,” the “Ligue contre le cancer-Hauts de Seine,” and European Union 7th Framework Program grant 305259.
Microvascular invasion (MiVI) is a major risk factor in postoperative tumor recurrence and mortality in hepatocellular carcinoma (HCC). Unfortunately, this histological feature is usually missed by liver biopsy because of limited sampling, and MiVI is commonly detected only after surgery and examination of the full resected specimen. To date, there exists no reliable tool for identifying MiVI prior to surgical procedures. This study aimed to compare the proteome of HCC with and without MiVI in order to identify surrogate biomarkers of MiVI. A training cohort comprising surgically resected primary HCC with MiVI (n = 30) and without MiVI (n = 26) was subjected to matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI IMS). Comparative analysis of acquired mass spectra of the two groups yielded 30 differential protein peaks, among which 28 were more strongly expressed in HCC with MiVI. Among these, two peaks were identified as N-term acetylated histone H4 dimethylated at lysine (K) 20, and N-term acetylated histone H4 dimethylated at K20 and acetylated at K16. Both peaks were validated in the training cohort and in an independent validation cohort (n = 23) by immunohistochemistry and western blot. Conclusion: These results demonstrate the potential of MALDI IMS for uncovering new relevant biomarkers of MiVI in HCC, and highlight the role of epigenetic modifications in the prognosis of HCC. Preoperative detection of modified forms of histone H4 expression in tumor biopsies would be helpful in management of patients with HCC. (Hepatology 2013;53:983–994)