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Histone H1.0—a potential molecular marker with prognostic value for patients with malignant gliomas

Abstract

Background

Histones are proteins closely associated with the DNA molecules and serve as a structural scaffold for the organization of chromatin. They play an important role in the regulation of gene expression by changing the level of DNA compaction.

The special subtype of the linker histone family—H1 zero (H1.0) is generally expressed in non-dividing, terminally differentiated cells.

The aim of our study is to investigate the correlation between the quantities of histone H1.0 in human gliomas, the histopathological grade and the overall survival.

Material and method

Twenty-nine (N = 29) patients with intraaxial lesions underwent a microsurgical tumor resection. Tumor samples were snap-frozen in liquid nitrogen immediately after resection.

Following a specific protocol, linker histones were extracted from the tumor specimens and the quantities of histone H1.0 were assessed. All patients were followed up prospectively.

Results

Of the 29 patients in our study (M:F = 17:12), five had a grade II astrocytoma, seven had a grade III, and 17 had a grade IV, according to the World Health Organization (WHO) classification.

At the end of the study, three patients were still alive.

The mean quantities of H1.0 were: 23.3 for grade II tumors, 13.9 for grade III and 11.3 for grade IV tumors.

The statistical analysis demonstrated that the histological grade, age and Karnofsky performance status (KPS) remain among the most reliable predictive factors for the survival of patients with gliomas.

Grade III–IV gliomas had significantly less histone H1.0 than grade II gliomas. Conformably, in a multivariate Cox regression analysis, H1.0 made a small but significant contribution (p < 0.05) to survival rates.

Conclusion

Our study confirmed that histone H1.0 is a potential biological marker with prognostic value for the survival of patients with gliomas. The quantities of histone H1.0 are correlated to the histopathological grade of the tumor. The more aggressive and malignant gliomas tend to have lower quantities of histone H1.0.

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Acknowledgements

N.G. is supported by the Bulgarian Science Fund, Grant number ТК02-468/2009.

M.G. is supported by the Bulgarian Science Fund, Grant number DMU 02/8 and from the World Federation of Scientists, National Scholarship Programme.

G. M. is supported by the Bulgarian Science Fund, Grant number DID 02/35.

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Correspondence to Nikolay Gabrovsky.

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Gabrovsky, N., Georgieva, M., Laleva, M. et al. Histone H1.0—a potential molecular marker with prognostic value for patients with malignant gliomas. Acta Neurochir 155, 1437–1442 (2013). https://doi.org/10.1007/s00701-013-1802-1

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  • DOI: https://doi.org/10.1007/s00701-013-1802-1

Keywords

  • Glioma
  • Histone
  • Epigenetics
  • Prognostic factors