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Expression and clinical significance of ERBB4 in gastric cancer
Xiaofeng Zhou1, Siyu Zhao2, Lin Zheng3
1Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Background:
Despite being the fourth leading cause of cancer deaths globally, advanced gastric cancer (GC) lacks effective therapeutic targets. While HER2-targeted therapy benefits a subset of patients, the role of its homolog ERBB4 remains controversial in GC pathogenesis and prognosis. This study aimed to examine the expression of ERBB4 in GC and explore whether it could serve as a new target for the biological therapy of GC.
Methods:
Sequencing and clinical data on the ERBB4 gene in GC (tumor) tissues and adjacent non-cancerous (normal) tissues were downloaded from The Cancer Genome Atlas (TCGA) database. A differential expression analysis of the collected ERBB4 gene expression data was conducted. The ERBB4 expression profile in GC was obtained from the Human Protein Atlas (HPA) database. The association between ERBB4 expression and GC prognosis was analyzed using the Kaplan-Meier plotter. The relationship between ERBB4 gene methylation and stomach adenocarcinoma (STAD) was examined online by MEXPRESS visualization in TCGA database. The correlation between ERBB4 messenger RNA (mRNA) expression and methylation/copy number variations (CNVs) was also examined by Spearman correlation analysis. ERBB4 expression microarray data were obtained from the Kaplan-Meier plotter database, and the ERBB4 expression survival curve was plotted. A Cox regression model was established to conduct univariate and multivariate analyses of the risk factors affecting patient prognosis.
Results:
Compared with adjacent non-cancerous tissues, ERBB4 mRNA and protein expression were significantly down-regulated in GC tissues. The mRNA expression level of the ERBB4 gene was affected by age, the sample type, and the risk of recurrence in GC patients. The abnormal amplification of ERBB4 was not correlated with its mRNA expression level. Additionally, there was a negative correlation between the methylation level and the mRNA expression of the ERBB4 gene. The Kaplan-Meier survival analysis revealed that patients with high ERBB4 expression had poor overall survival (OS) and progression-free survival (PFS) compared with those with low ERBB4 expression. The multivariate Cox regression analysis showed that ERBB4 was an independent prognostic factor for a poor prognosis in GC, but was not related to PFS.
Conclusions:
ERBB4 is an independent prognostic factor for OS and may serve as a novel target for molecular therapy in GC.
Insights
Epithelial cell adhesion molecule 4 (ERBB4) is downregulated in gastric cancer (GC). High ERBB4 expression indicates a poor prognosis and may represent a new therapeutic target for GC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer (GC) is a leading cause of cancer mortality with limited therapeutic options.
- While HER2-targeted therapy is used, the role of its homolog, ERBB4, in GC is unclear.
- This study investigates ERBB4 expression and its potential as a therapeutic target in GC.
Purpose of the Study:
- To examine ERBB4 expression in gastric cancer tissues and adjacent non-cancerous tissues.
- To explore the association between ERBB4 expression and GC patient prognosis.
- To evaluate ERBB4 as a potential target for biological therapy in GC.
Main Methods:
- Downloaded TCGA and HPA data for ERBB4 expression analysis in GC.
- Utilized Kaplan-Meier plotter for survival analysis and MEXPRESS for methylation analysis.
- Performed Spearman correlation and Cox regression analyses to assess ERBB4's prognostic significance.
Main Results:
- ERBB4 mRNA and protein expression were significantly downregulated in GC tissues compared to normal tissues.
- High ERBB4 expression correlated with poor overall survival (OS) and progression-free survival (PFS).
- ERBB4 was identified as an independent prognostic factor for poor OS in GC.
Conclusions:
- ERBB4 is significantly downregulated in gastric cancer.
- ERBB4 expression serves as an independent prognostic indicator for overall survival in GC patients.
- ERBB4 represents a potential novel molecular target for gastric cancer therapy.
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