Global histone modification pattern associated with recurrence and disease-free survival in non-small cell lung cancer patients

Joon Seon Song, Yongseok Kim, Dong Kwan Kim, Sung il Park, Se Jin Jang

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Global histone modification patterns are presumed to establish epigenetic patterns of gene expression and determine the biology of the cell. In the present study, the global modification status of histone H3 and H4 was evaluated in 408 non-small cell lung cancer (NSCLC) tissues by immunostaining. NSCLC showed variable staining scores for each antibody. Clinicopathological analyses demonstrated a positive correlation between weak nuclear staining for H3K9Ac (P < 0.001), H3K9TriMe (P= 0.001), H4K16Ac (P < 0.001) and tumor recurrence except H4K20 TriMe (P= 0.201). Staining scores of four different antibodies were not correlated with other clinicopathologic variables. Patients were further clustered according to histone modification patterns: acetylation dominant, methylation dominant, co-dominant and modification-negative. The acetylation-dominant group (P= 0.009) and co-dominant group exhibited less frequent lymph node metastasis (P= 0.050), recurrence (P= 0.002) and distant metastasis (P= 0.010). The acetylation-dominant group showed better prognosis in survival analysis (P < 0.001, log-rank), whereas methylation-dominant and modification-negative status was associated with poor prognosis. In conclusion, our data suggest that global histone H3 and H4 modification patterns are potential markers of tumor recurrence and disease-free survival in NSCLC patients.

Original languageEnglish
Pages (from-to)182-190
Number of pages9
JournalPathology International
Volume62
Issue number3
DOIs
StatePublished - 2012 Mar 1

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Histone Code
Non-Small Cell Lung Carcinoma
Histones
Disease-Free Survival
Acetylation
Recurrence
Staining and Labeling
Methylation
Neoplasm Metastasis
Antibodies
Survival Analysis
Tumor Biomarkers
Epigenomics
Cell Biology
Lymph Nodes
Gene Expression
Neoplasms

Keywords

  • Acetylation
  • Histone
  • Methylation
  • Non-small cell lung cancer
  • Recurrence

Cite this

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abstract = "Global histone modification patterns are presumed to establish epigenetic patterns of gene expression and determine the biology of the cell. In the present study, the global modification status of histone H3 and H4 was evaluated in 408 non-small cell lung cancer (NSCLC) tissues by immunostaining. NSCLC showed variable staining scores for each antibody. Clinicopathological analyses demonstrated a positive correlation between weak nuclear staining for H3K9Ac (P < 0.001), H3K9TriMe (P= 0.001), H4K16Ac (P < 0.001) and tumor recurrence except H4K20 TriMe (P= 0.201). Staining scores of four different antibodies were not correlated with other clinicopathologic variables. Patients were further clustered according to histone modification patterns: acetylation dominant, methylation dominant, co-dominant and modification-negative. The acetylation-dominant group (P= 0.009) and co-dominant group exhibited less frequent lymph node metastasis (P= 0.050), recurrence (P= 0.002) and distant metastasis (P= 0.010). The acetylation-dominant group showed better prognosis in survival analysis (P < 0.001, log-rank), whereas methylation-dominant and modification-negative status was associated with poor prognosis. In conclusion, our data suggest that global histone H3 and H4 modification patterns are potential markers of tumor recurrence and disease-free survival in NSCLC patients.",
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Global histone modification pattern associated with recurrence and disease-free survival in non-small cell lung cancer patients. / Song, Joon Seon; Kim, Yongseok; Kim, Dong Kwan; Park, Sung il; Jang, Se Jin.

In: Pathology International, Vol. 62, No. 3, 01.03.2012, p. 182-190.

Research output: Contribution to journalArticle

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