SIRT7, H3K18ac, and ELK4 immunohistochemical expression in hepatocellular carcinoma

Hye Seung Lee, Wonkyung Jung, Eunjung Lee, Hyeyoon Chang, Jin Hyuk Choi, Han Gyeom Kim, Aeree Kim, Baek-Hui Kim

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: SIRT7 is one of the histone deacetylases and is NAD-dependent. It forms a complex with ETS-like transcription factor 4 (ELK4), which deacetylates H3K18ac and works as a transcriptional suppressor. Overexpression of SIRT7 and deacetylation of H3K18ac have been shown to be associated with aggressive clinical behavior in some cancers, including hepatocellular carcinoma (HCC). The present study investigated the immunohistochemical expression of SIRT7, H3K18ac, and ELK4 in hepatocellular carcinoma. Methods: A total of 278 HCC patients were enrolled in this study. Tissue microarray blocks were made from existing paraffin-embedded blocks. Immunohistochemical expressions of SIRT7, H3K18ac and ELK4 were scored and analyzed. Results: High SIRT7 (p = .034), high H3K18ac (p = .001), and low ELK4 (p = .021) groups were associated with poor outcomes. Age < 65 years (p = .028), tumor size = 5 cm (p = .001), presence of vascular emboli (p = .003), involvement of surgical margin (p = .001), and high American Joint Committee on Cancer stage (III & V) (p < .001) were correlated with worse prognoses. In multivariate analysis, H3K18ac (p = .001) and ELK4 (p = .015) were the significant independent prognostic factors. Conclusions: High SIRT7 expression with poor overall survival implies that deacetylation of H3K18ac contributes to progression of HCC. High H3K18ac expression with poor prognosis is predicted due to a compensation mechanism. In addition, high ELK4 expression with good prognosis suggests another role of ELK4 as a tumor suppressor beyond SIRT7's helper. In conclusion, we could assume that the H3K18ac deacetylation pathway is influenced by many other factors.

Original languageEnglish
Pages (from-to)337-344
Number of pages8
JournalJournal of Pathology and Translational Medicine
Volume50
Issue number5
DOIs
Publication statusPublished - 2016

Fingerprint

Hepatocellular Carcinoma
Transcription Factors
Group III Histone Deacetylases
Neoplasms
Embolism
Paraffin
Blood Vessels
Multivariate Analysis
Survival

Keywords

  • Carcinoma
  • ELK4
  • H3K18ac
  • Hepatocellular
  • Immunohistochemistry
  • Sirtuin 7 protein

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

SIRT7, H3K18ac, and ELK4 immunohistochemical expression in hepatocellular carcinoma. / Lee, Hye Seung; Jung, Wonkyung; Lee, Eunjung; Chang, Hyeyoon; Choi, Jin Hyuk; Kim, Han Gyeom; Kim, Aeree; Kim, Baek-Hui.

In: Journal of Pathology and Translational Medicine, Vol. 50, No. 5, 2016, p. 337-344.

Research output: Contribution to journalArticle

Lee, Hye Seung ; Jung, Wonkyung ; Lee, Eunjung ; Chang, Hyeyoon ; Choi, Jin Hyuk ; Kim, Han Gyeom ; Kim, Aeree ; Kim, Baek-Hui. / SIRT7, H3K18ac, and ELK4 immunohistochemical expression in hepatocellular carcinoma. In: Journal of Pathology and Translational Medicine. 2016 ; Vol. 50, No. 5. pp. 337-344.
@article{bd61478b9f7a4e7ab44d10ebf7e6d786,
title = "SIRT7, H3K18ac, and ELK4 immunohistochemical expression in hepatocellular carcinoma",
abstract = "Background: SIRT7 is one of the histone deacetylases and is NAD-dependent. It forms a complex with ETS-like transcription factor 4 (ELK4), which deacetylates H3K18ac and works as a transcriptional suppressor. Overexpression of SIRT7 and deacetylation of H3K18ac have been shown to be associated with aggressive clinical behavior in some cancers, including hepatocellular carcinoma (HCC). The present study investigated the immunohistochemical expression of SIRT7, H3K18ac, and ELK4 in hepatocellular carcinoma. Methods: A total of 278 HCC patients were enrolled in this study. Tissue microarray blocks were made from existing paraffin-embedded blocks. Immunohistochemical expressions of SIRT7, H3K18ac and ELK4 were scored and analyzed. Results: High SIRT7 (p = .034), high H3K18ac (p = .001), and low ELK4 (p = .021) groups were associated with poor outcomes. Age < 65 years (p = .028), tumor size = 5 cm (p = .001), presence of vascular emboli (p = .003), involvement of surgical margin (p = .001), and high American Joint Committee on Cancer stage (III & V) (p < .001) were correlated with worse prognoses. In multivariate analysis, H3K18ac (p = .001) and ELK4 (p = .015) were the significant independent prognostic factors. Conclusions: High SIRT7 expression with poor overall survival implies that deacetylation of H3K18ac contributes to progression of HCC. High H3K18ac expression with poor prognosis is predicted due to a compensation mechanism. In addition, high ELK4 expression with good prognosis suggests another role of ELK4 as a tumor suppressor beyond SIRT7's helper. In conclusion, we could assume that the H3K18ac deacetylation pathway is influenced by many other factors.",
keywords = "Carcinoma, ELK4, H3K18ac, Hepatocellular, Immunohistochemistry, Sirtuin 7 protein",
author = "Lee, {Hye Seung} and Wonkyung Jung and Eunjung Lee and Hyeyoon Chang and Choi, {Jin Hyuk} and Kim, {Han Gyeom} and Aeree Kim and Baek-Hui Kim",
year = "2016",
doi = "10.4132/jptm.2016.05.20",
language = "English",
volume = "50",
pages = "337--344",
journal = "Journal of Pathology and Translational Medicine",
issn = "2383-7837",
publisher = "Korean Society of Pathologists",
number = "5",

}

TY - JOUR

T1 - SIRT7, H3K18ac, and ELK4 immunohistochemical expression in hepatocellular carcinoma

AU - Lee, Hye Seung

AU - Jung, Wonkyung

AU - Lee, Eunjung

AU - Chang, Hyeyoon

AU - Choi, Jin Hyuk

AU - Kim, Han Gyeom

AU - Kim, Aeree

AU - Kim, Baek-Hui

PY - 2016

Y1 - 2016

N2 - Background: SIRT7 is one of the histone deacetylases and is NAD-dependent. It forms a complex with ETS-like transcription factor 4 (ELK4), which deacetylates H3K18ac and works as a transcriptional suppressor. Overexpression of SIRT7 and deacetylation of H3K18ac have been shown to be associated with aggressive clinical behavior in some cancers, including hepatocellular carcinoma (HCC). The present study investigated the immunohistochemical expression of SIRT7, H3K18ac, and ELK4 in hepatocellular carcinoma. Methods: A total of 278 HCC patients were enrolled in this study. Tissue microarray blocks were made from existing paraffin-embedded blocks. Immunohistochemical expressions of SIRT7, H3K18ac and ELK4 were scored and analyzed. Results: High SIRT7 (p = .034), high H3K18ac (p = .001), and low ELK4 (p = .021) groups were associated with poor outcomes. Age < 65 years (p = .028), tumor size = 5 cm (p = .001), presence of vascular emboli (p = .003), involvement of surgical margin (p = .001), and high American Joint Committee on Cancer stage (III & V) (p < .001) were correlated with worse prognoses. In multivariate analysis, H3K18ac (p = .001) and ELK4 (p = .015) were the significant independent prognostic factors. Conclusions: High SIRT7 expression with poor overall survival implies that deacetylation of H3K18ac contributes to progression of HCC. High H3K18ac expression with poor prognosis is predicted due to a compensation mechanism. In addition, high ELK4 expression with good prognosis suggests another role of ELK4 as a tumor suppressor beyond SIRT7's helper. In conclusion, we could assume that the H3K18ac deacetylation pathway is influenced by many other factors.

AB - Background: SIRT7 is one of the histone deacetylases and is NAD-dependent. It forms a complex with ETS-like transcription factor 4 (ELK4), which deacetylates H3K18ac and works as a transcriptional suppressor. Overexpression of SIRT7 and deacetylation of H3K18ac have been shown to be associated with aggressive clinical behavior in some cancers, including hepatocellular carcinoma (HCC). The present study investigated the immunohistochemical expression of SIRT7, H3K18ac, and ELK4 in hepatocellular carcinoma. Methods: A total of 278 HCC patients were enrolled in this study. Tissue microarray blocks were made from existing paraffin-embedded blocks. Immunohistochemical expressions of SIRT7, H3K18ac and ELK4 were scored and analyzed. Results: High SIRT7 (p = .034), high H3K18ac (p = .001), and low ELK4 (p = .021) groups were associated with poor outcomes. Age < 65 years (p = .028), tumor size = 5 cm (p = .001), presence of vascular emboli (p = .003), involvement of surgical margin (p = .001), and high American Joint Committee on Cancer stage (III & V) (p < .001) were correlated with worse prognoses. In multivariate analysis, H3K18ac (p = .001) and ELK4 (p = .015) were the significant independent prognostic factors. Conclusions: High SIRT7 expression with poor overall survival implies that deacetylation of H3K18ac contributes to progression of HCC. High H3K18ac expression with poor prognosis is predicted due to a compensation mechanism. In addition, high ELK4 expression with good prognosis suggests another role of ELK4 as a tumor suppressor beyond SIRT7's helper. In conclusion, we could assume that the H3K18ac deacetylation pathway is influenced by many other factors.

KW - Carcinoma

KW - ELK4

KW - H3K18ac

KW - Hepatocellular

KW - Immunohistochemistry

KW - Sirtuin 7 protein

UR - http://www.scopus.com/inward/record.url?scp=84992437245&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84992437245&partnerID=8YFLogxK

U2 - 10.4132/jptm.2016.05.20

DO - 10.4132/jptm.2016.05.20

M3 - Article

AN - SCOPUS:84992437245

VL - 50

SP - 337

EP - 344

JO - Journal of Pathology and Translational Medicine

JF - Journal of Pathology and Translational Medicine

SN - 2383-7837

IS - 5

ER -