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Updated: Apr 11, 2026
Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
Sirtuin-4 (SIRT4) is downregulated and associated with some clinicopathological features in gastric adenocarcinoma
Guoyu Huang1, Feifei Cui1, Fudong Yu1
1Department of General Surgery, First People's Hospital, Shanghai Jiao Tong Univerisity, 85 Wujin Road, Shanghai 200080, China.
Background:
Several members of the SIRT family (SIRT1-7), which are a highly conserved family of NAD(+)-dependent enzymes, play an important role in tumor formation. Recently, several studies have suggested that SIRT4 can regulate glutamine metabolism yet have tumor suppressor function too. However, our understanding of SIRT4 expression and its association with the clinicopathological parameters remains poor.
Method:
We evaluated SIRT4 protein expression levels in gastric adenocarcinoma and corresponding normal gastric tissue by immunohistochemical staining on a tissue microarray that included 75 gastric adenocarcinoma patients. We also determined the association between SIRT4 expression levels and selected clinicopathological parameters in gastric adenocarcinoma.
Results:
We found that the expression level of SIRT4 in gastric adenocarcinoma was significantly lower than the corresponding normal tissue levels (P=0.003). Besides, lower SIRT4 levels were observed in pathological grade (P=0.002), depth of tumor invasion (P=0.034), positive lymph node numbers (P=0.005) and UICC stage (P=0.002).
Conclusions:
Our results support the notion that SIRT4 behaves as a tumor suppressor at the human tissue protein level. In addition, our data indicate that SIRT4 might be closely involved in the process of gastric adenocarcinoma development and it might potentially serve as a diagnostic biomarker and therapeutic target in gastric adenocarcinoma.
Insights
SIRT4, a tumor suppressor, is significantly lower in gastric adenocarcinoma tissues compared to normal tissues. Reduced SIRT4 expression correlates with advanced disease, suggesting its potential as a diagnostic biomarker and therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Sirtuins (SIRTs) are NAD(+)-dependent enzymes crucial in tumor formation.
- SIRT4 is implicated in glutamine metabolism and possesses tumor suppressor functions.
- Limited understanding exists regarding SIRT4 expression and its clinicopathological correlations in gastric cancer.
Purpose of the Study:
- To investigate SIRT4 protein expression in gastric adenocarcinoma.
- To determine the association between SIRT4 levels and clinicopathological parameters in gastric adenocarcinoma.
Main Methods:
- Immunohistochemical staining of SIRT4 protein on tissue microarrays from 75 gastric adenocarcinoma patients.
- Analysis of SIRT4 expression in tumor tissues versus adjacent normal gastric tissues.
- Correlation analysis between SIRT4 expression and clinicopathological features.
Main Results:
- SIRT4 protein expression was significantly lower in gastric adenocarcinoma compared to normal gastric tissues (P=0.003).
- Lower SIRT4 levels correlated with higher pathological grade (P=0.002), deeper tumor invasion (P=0.034), more positive lymph nodes (P=0.005), and advanced UICC stage (P=0.002).
Conclusions:
- SIRT4 functions as a tumor suppressor in human gastric tissues.
- SIRT4 is involved in gastric adenocarcinoma development.
- SIRT4 may serve as a potential diagnostic biomarker and therapeutic target for gastric adenocarcinoma.
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