HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Imaging mass spectrometry reveals modified forms of histone H4 as new biomarkers of microvascular invasion in hepatocellular carcinomas.

AbstractUNLABELLED:
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.
AuthorsNicolas Poté, Theodore Alexandrov, Julie Le Faouder, Samira Laouirem, Thibaut Léger, Mouniya Mebarki, Jacques Belghiti, Jean-Michel Camadro, Pierre Bedossa, Valérie Paradis
JournalHepatology (Baltimore, Md.) (Hepatology) Vol. 58 Issue 3 Pg. 983-94 (Sep 2013) ISSN: 1527-3350 [Electronic] United States
PMID23553687 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2013 by the American Association for the Study of Liver Diseases.
Chemical References
  • Biomarkers, Tumor
  • Histones
Topics
  • Aged
  • Biomarkers, Tumor (metabolism)
  • Biopsy
  • Carcinoma, Hepatocellular (blood supply, metabolism, pathology)
  • Cohort Studies
  • Disease Management
  • Female
  • Histones (metabolism)
  • Humans
  • Liver Neoplasms (blood supply, metabolism, pathology)
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local (epidemiology, metabolism)
  • Neovascularization, Pathologic (metabolism)
  • Prognosis
  • Risk Factors
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization (methods)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: