Effect of EGFR and p-AKT Overexpression on Chromosomal Instability in Gastric Cancer
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Published on: September 15, 2023
Yuichi Hisamatsu1, Eiji Oki2, Hajime Otsu1
1Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Background:
Molecular profiling in gastric cancer (GC) is important for diagnosis and treatment. In this study, we investigated signal transduction pathways that might induce chromosomal instability in GC.
Methods:
Epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and p-AKT expression were analyzed using immunohistochemistry, and chromosomal instability was assessed by DNA aneuploidy using laser scanning cytometry, in a total of 202 GC cases.
Results:
The rate of EGFR expression and p-AKT expression was 70.3 and 34.2 %, respectively, in GC patients. In total, 57.5 % of GC patients exhibited DNA aneuploidy, and p-AKT positively correlated with EGFR and HER2 (p = 0.0127 and p = 0.00031, respectively). Patients with EGFR overexpressing GC showed shorter disease-specific survival than the other cases (hazard ratio 2.00, 95 % confidence interval 1.19-3.53; p = 0.0104). Moreover, EGFR and p-AKT expression was significantly correlated with DNA aneuploidy (p = 0.0002 and p = 0.0302, respectively).
Conclusions:
Our data showed that both EGFR and p-AKT overexpression were clearly associated with DNA aneuploidy. Aneuploidy could be a useful marker for therapies that target EGFR.
Insights
Overexpression of epidermal growth factor receptor (EGFR) and p-AKT in gastric cancer (GC) is linked to DNA aneuploidy. This finding suggests aneuploidy may guide therapies targeting EGFR in GC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Molecular profiling is crucial for gastric cancer (GC) diagnosis and treatment.
- Investigating signal transduction pathways is key to understanding GC chromosomal instability.
Purpose of the Study:
- To explore the association between signal transduction pathways and chromosomal instability in GC.
- To determine the role of EGFR, HER2, and p-AKT in GC pathogenesis and survival.
Main Methods:
- Analyzed EGFR, HER2, and p-AKT expression via immunohistochemistry in 202 GC cases.
- Assessed chromosomal instability using DNA aneuploidy via laser scanning cytometry.
Main Results:
- EGFR and p-AKT overexpression occurred in 70.3% and 34.2% of GC patients, respectively.
- DNA aneuploidy was present in 57.5% of GC patients.
- EGFR and p-AKT expression positively correlated with DNA aneuploidy (p<0.001) and with each other (p<0.013).
- EGFR overexpression was linked to shorter disease-specific survival (HR 2.00, p=0.0104).
Conclusions:
- EGFR and p-AKT overexpression are significantly associated with DNA aneuploidy in GC.
- DNA aneuploidy may serve as a predictive biomarker for EGFR-targeted therapies in gastric cancer.
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