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タイトル: | Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: Results of a multicenter study |
著者: | Baba, Hideo Baba, Yoshifumi Uemoto, Shinji Yoshida, Kazuhiro Saiura, Akio Watanabe, Masayuki Maehara, Yoshihiko Oki, Eiji Ikeda, Yasuharu Matsuda, Hiroyuki Yamamoto, Masakazu Shimada, Mitsuo Taketomi, Akinobu Unno, Michiaki Sugihara, Kenichi Ogata, Yutaka Eguchi, Susumu Kitano, Seigo Shirouzu, Kazuo Saiki, Yasumitsu Takamori, Hiroshi Mori, Masaki Hirata, Toshihiko Wakabayashi, Go Kokudo, Norihiro |
著者名の別形: | 上本, 伸二 |
キーワード: | ERCC1 DPYD VEGFA colorectal cancer bevacizumab |
発行日: | 19-Aug-2015 |
出版者: | Impact Journals LLC |
誌名: | Oncotarget |
巻: | 6 |
号: | 32 |
開始ページ: | 34004 |
終了ページ: | 34013 |
抄録: | Our previous study showed that administering oxaliplatin as first-line chemotherapy increased ERCC1 and DPD levels in liver colorectal cancers (CRCs) metastases. Second, whether the anti-VEGF monoclonal antibody bevacizumab alters tumoral VEGFA levels is unknown. We conducted this multicenter observational study to validate our previous findings on ERCC1 and DPD, and clarify the response of VEGFA expression to bavacizumab administration. 346 CRC patients with liver metastases were enrolled at 22 Japanese institutes. Resected liver metastases were available for 175 patients previously treated with oxaliplatin-based chemotherapy (chemotherapy group) and 171 receiving no previous chemotherapy (non-chemotherapy group). ERCC1, DPYD, and VEGFA mRNA levels were measured by real-time RT-PCR. ERCC1 mRNA expression was significantly higher in the chemotherapy group than in the non-chemotherapy group (P = 0.033), and were significantly correlated (Spearman's correlation coefficient = 0.42; P < 0.0001). VEGFA expression level was higher in patients receiving bevacizumab (n = 51) than in those who did not (n = 251) (P = 0.007). This study confirmed that first-line oxaliplatin-based chemotherapy increases ERCC1 and DPYD 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. |
著作権等: | All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. |
URI: | http://hdl.handle.net/2433/216052 |
DOI(出版社版): | 10.18632/oncotarget.5227 |
PubMed ID: | 26372896 |
出現コレクション: | 学術雑誌掲載論文等 |
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