Changes in expression levels of ERCC1, DPD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670588
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: BABA hideo 熊本大学, 大学院生命科学研究部, 教授 (20240905)
• Co-Investigator(Kenkyū-buntansha): BABA Yoshifumi 熊本大学, 大学院生命科学研究部, 講師 (20599708)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: ERCC1 / DPD / VEGFA / 大腸癌 / 化学療法 / バイオマーカー

Outline of Final Research Achievements

Our previous study showed that administering oxaliplatin as first-line chemotherapy increased expression levels of ERCC1and DPD in liver CRC metastases. Second, whether the anti-VEGF monoclonal antibody bevacizumab alters tumoral VEGFA levels is unknown. We conducted this study to validate our previous findings on ERCC1 and DPD, and clarifiy the response of tumoral VEGFA expression to bavacizumab administration. ERCC1 mRNA expression was significantly higher in the chemotherapy group than in the non-chemotherapy group, and were significantly correlated. VEGFA expression level was higher in patients receiving bevacizumab than in those who did not. This study confirmed that first-line oxaliplatin-based chemotherapy increases ERCC1 and DPD expression levels, potentially enhancing chemosensitivity to subsequent therapy. We also found that bevacizumab induces VEGFA expression in tumor cells, suggesting a biologic rationale for extending bevacizumab treatment beyond first progression.

Free Research Field

消化器外科学