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Updated: Jul 12, 2025
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
VEGFA Status as a Predictive Marker of Therapy Outcome in Metastatic Gastric Cancer Patients Following
Annalisa Schirizzi1, Aram Arshadi2, Doron Tolomeo2
1Laboratory of Experimental Oncology, National Institute of Gastroenterology, IRCCS "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Italy.
Abstract:
Metastatic gastric cancer (mGC) often has a poor prognosis and may benefit from a few targeted therapies. Ramucirumab-based anti-angiogenic therapy targeting the VEGFR2 represents a milestone in the second-line treatment of mGC. Several studies on different cancers are focusing on the major VEGFR2 ligand status, meaning VEGFA gene copy number and protein overexpression, as a prognostic marker and predictor of response to anti-angiogenic therapy. Following this insight, our study aims to examine the role of VEGFA status as a predictive biomarker for the outcome of second-line therapy with Ramucirumab and paclitaxel in mGC patients. To this purpose, the copy number of the VEGFA gene, by fluorescence in situ hybridization experiments, and its expression in tumor tissue as well as the density of micro-vessels, by immunohistochemistry experiments, were assessed in samples derived from mGC patients. This analysis found that amplification of VEGFA concomitantly with VEGFA overexpression and overexpression of VEGFA with micro-vessels density are more represented in patients showing disease control during treatment with Ramucirumab. In addition, in the analyzed series, it was found that amplification was not always associated with overexpression of VEGFA, but overexpression of VEGFA correlates with high micro-vessel density. In conclusion, overexpression of VEGFA could emerge as a potential biomarker to predict the response to anti-angiogenic therapy.
Insights
Vascular Endothelial Growth Factor A (VEGFA) overexpression may predict patient response to ramucirumab therapy in metastatic gastric cancer. This finding offers a potential biomarker for anti-angiogenic treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Biomarkers
Background:
- Metastatic gastric cancer (mGC) presents a poor prognosis, with limited targeted therapy options.
- Ramucirumab, targeting VEGFR2, is a key second-line anti-angiogenic therapy for mGC.
- VEGFA status (gene copy number, protein overexpression) is explored as a prognostic and predictive marker for anti-angiogenic therapies.
Purpose of the Study:
- To investigate VEGFA status as a predictive biomarker for ramucirumab and paclitaxel second-line therapy outcomes in mGC patients.
- To correlate VEGFA gene copy number and protein expression with treatment response.
- To assess the relationship between VEGFA status, micro-vessel density, and disease control.
Main Methods:
- Assessed VEGFA gene copy number using fluorescence in situ hybridization (FISH).
- Evaluated VEGFA protein expression and tumor micro-vessel density via immunohistochemistry (IHC).
- Analyzed samples from mGC patients undergoing second-line ramucirumab treatment.
Main Results:
- VEGFA gene amplification with concomitant overexpression, and VEGFA overexpression with high micro-vessel density, were more frequent in patients achieving disease control.
- VEGFA gene amplification did not consistently correlate with VEGFA overexpression.
- VEGFA overexpression showed a correlation with increased tumor micro-vessel density.
Conclusions:
- VEGFA overexpression may serve as a predictive biomarker for response to ramucirumab-based anti-angiogenic therapy in mGC.
- VEGFA status warrants further investigation for guiding treatment decisions in metastatic gastric cancer.
- High micro-vessel density is associated with VEGFA overexpression in this patient cohort.
