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Updated: Mar 16, 2026
Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
Published on: April 12, 2024
SIRT7, H3K18ac, and ELK4 Immunohistochemical Expression in Hepatocellular Carcinoma
Hye Seung Lee1, Wonkyung Jung1, Eunjung Lee2
1Department of Pathology, Korea University Guro Hospital, Seoul, Korea.
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.
Insights
High SIRT7 and H3K18ac expression correlate with poor outcomes in hepatocellular carcinoma (HCC) patients, while ELK4 shows a protective role. These findings highlight potential therapeutic targets for aggressive HCC.
Area of Science:
- Molecular oncology
- Epigenetics
- Cancer biomarkers
Background:
- SIRT7, a histone deacetylase, complexes with ELK4 to suppress transcription via H3K18ac deacetylation.
- Overexpression of SIRT7 and H3K18ac deacetylation are linked to aggressive hepatocellular carcinoma (HCC).
Purpose of the Study:
- To investigate the immunohistochemical expression of SIRT7, H3K18ac, and ELK4 in HCC.
- To correlate these expressions with clinical behavior and patient prognosis.
Main Methods:
- Analysis of 278 HCC patients using tissue microarrays.
- Immunohistochemical scoring and statistical analysis of SIRT7, H3K18ac, and ELK4 expression levels.
Main Results:
- High SIRT7 and high H3K18ac expression were associated with poor patient outcomes (p = .034 and p = .001, respectively).
- Low ELK4 expression correlated with worse prognosis (p = .021).
- H3K18ac and ELK4 were identified as significant independent prognostic factors in multivariate analysis (p = .001 and p = .015, respectively).
Conclusions:
- Deacetylation of H3K18ac by SIRT7 contributes to HCC progression, indicated by high SIRT7 and poor survival.
- High H3K18ac expression suggests a compensatory mechanism driving poor prognosis.
- ELK4 may function as a tumor suppressor, with high expression correlating with good prognosis, indicating a complex regulatory pathway.
