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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)34004-34013
Number of pages10
JournalOncotarget
Volume6
Issue number32
DOIs
Publication statusPublished - Jan 1 2015

Fingerprint

oxaliplatin
Multicenter Studies
Colorectal Neoplasms
Drug Therapy
Messenger RNA
Neoplasm Metastasis
Liver
Liver Neoplasms
Vascular Endothelial Growth Factor A
Observational Studies
Real-Time Polymerase Chain Reaction
Monoclonal Antibodies
Bevacizumab
Therapeutics
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

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

In: Oncotarget, Vol. 6, No. 32, 01.01.2015, p. 34004-34013.

Research output: Contribution to journalArticle

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, Saiki, Y, Takamori, H, Mori, M, Hirata, T, Wakabayashi, G & 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, vol. 6, no. 32, pp. 34004-34013. https://doi.org/10.18632/oncotarget.5227
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. / Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer : Results of a multicenter study. In: Oncotarget. 2015 ; Vol. 6, No. 32. pp. 34004-34013.
@article{cba497903c984c7ca74b536f75d02841,
title = "Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: Results of a multicenter study",
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.",
author = "Hideo Baba and Yoshifumi Baba and Shinji Uemoto and Kazuhiro Yoshida and Akio Saiura and Masayuki Watanabe and Yoshihiko Maehara and Eiji Oki and Yasuharu Ikeda and Hiroyuki Matsuda and Masakazu Yamamoto and Mitsuo Shimada and Akinobu Taketomi and Michiaki Unno and Kenichi Sugihara and Yutaka Ogata and Susumu Eguchi and Seigo Kitano and Kazuo Shirouzu and Yasumitsu Saiki and Hiroshi Takamori and Masaki Mori and Toshihiko Hirata and Go Wakabayashi and Norihiro Kokudo",
year = "2015",
month = "1",
day = "1",
doi = "10.18632/oncotarget.5227",
language = "English",
volume = "6",
pages = "34004--34013",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "32",

}

TY - JOUR

T1 - Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer

T2 - Results of a multicenter study

AU - Baba, Hideo

AU - Baba, Yoshifumi

AU - Uemoto, Shinji

AU - Yoshida, Kazuhiro

AU - Saiura, Akio

AU - Watanabe, Masayuki

AU - Maehara, Yoshihiko

AU - Oki, Eiji

AU - Ikeda, Yasuharu

AU - Matsuda, Hiroyuki

AU - Yamamoto, Masakazu

AU - Shimada, Mitsuo

AU - Taketomi, Akinobu

AU - Unno, Michiaki

AU - Sugihara, Kenichi

AU - Ogata, Yutaka

AU - Eguchi, Susumu

AU - Kitano, Seigo

AU - Shirouzu, Kazuo

AU - Saiki, Yasumitsu

AU - Takamori, Hiroshi

AU - Mori, Masaki

AU - Hirata, Toshihiko

AU - Wakabayashi, Go

AU - Kokudo, Norihiro

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84946097535&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84946097535&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.5227

DO - 10.18632/oncotarget.5227

M3 - Article

C2 - 26372896

AN - SCOPUS:84946097535

VL - 6

SP - 34004

EP - 34013

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 32

ER -