Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: Results of a multicenter study

Hideo Baba, Yoshifumi Baba, Shinji Uemoto, Kazuhiro Yoshida, Akio Saiura, Masayuki Watanabe, Yoshihiko Maehara, Eiji Oki, Yasuharu Ikeda, Hiroyuki Matsuda, Masakazu Yamamoto, Mitsuo Shimada, Akinobu Taketomi, Michiaki Unno, Kenichi Sugihara, Yutaka Ogata, Susumu Eguchi, Seigo Kitano, Kazuo Shirouzu, Yasumitsu SaikiHiroshi Takamori, Masaki Mori, Toshihiko Hirata, Go Wakabayashi, Norihiro Kokudo

研究成果: Contribution to journalArticle

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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.

元の言語英語
ページ(範囲)34004-34013
ページ数10
ジャーナルOncotarget
6
発行部数32
DOI
出版物ステータス出版済み - 2015

All Science Journal Classification (ASJC) codes

  • Oncology

フィンガープリント Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: Results of a multicenter study' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Baba, H., Baba, Y., Uemoto, S., Yoshida, K., Saiura, A., Watanabe, M., Maehara, Y., Oki, E., Ikeda, Y., Matsuda, H., Yamamoto, M., Shimada, M., Taketomi, A., Unno, M., Sugihara, K., Ogata, Y., Eguchi, S., Kitano, S., Shirouzu, K., ... Kokudo, N. (2015). Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: Results of a multicenter study. Oncotarget, 6(32), 34004-34013. https://doi.org/10.18632/oncotarget.5227