Oncotarget

Clinical Research Papers:

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 Saiki, Hiroshi Takamori, Masaki Mori, Toshihiko Hirata, Go Wakabayashi and Norihiro Kokudo

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Oncotarget. 2015; 6:34004-34013. https://doi.org/10.18632/oncotarget.5227

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Abstract

Hideo Baba1,*, Yoshifumi Baba1,*, Shinji Uemoto2, Kazuhiro Yoshida3, Akio Saiura4, Masayuki Watanabe4, Yoshihiko Maehara5, Eiji Oki5, Yasuharu Ikeda6, Hiroyuki Matsuda7, Masakazu Yamamoto8, Mitsuo Shimada9, Akinobu Taketomi10, Michiaki Unno11, Kenichi Sugihara12, Yutaka Ogata13, Susumu Eguchi14, Seigo Kitano15, Kazuo Shirouzu16, Yasumitsu Saiki17, Hiroshi Takamori18, Masaki Mori19, Toshihiko Hirata20, Go Wakabayashi21 and Norihiro Kokudo22

1 Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan

2 Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

3 Department of Surgical Oncology, Gifu Graduate School of Medicine, Gifu, Japan

4 Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

5 Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

6 Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

7 Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan

8 Department of Surgery, Tokyo Women’s Medical University, Tokyo, Japan

9 Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan

10 Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan

11 Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan

12 Department of Surgical Oncology, Tokyo Medical and Dental University, Tokyo, Japan

13 Department of Surgery, Kurume University Medical Center, Kurume, Japan

14 Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

15 Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Oita, Japan

16 Department of Surgery, Kurume University School of Medicine, Kurume, Japan

17 Coloproctology Center, Takano Hospital, Kumamoto, Japan

18 Department of Surgery, Saiseikai Kumamoto Hospital, Kumamoto, Japan

19 Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan

20 Department of Surgery, Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan

21 Department of Surgery, Iwate Medical University, School of Medicine, Morioka, Japan

22 Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

* These authors have contributed equally to this work

Correspondence to:

Hideo Baba, email:

Keywords: ERCC1, DPYD, VEGFA, colorectal cancer, bevacizumab

Received: July 18, 2015 Accepted: August 12, 2015 Published: August 19, 2015

Abstract

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.


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