A newly established monoclonal antibody against ERCC1 detects major isoforms of ERCC1 in gastric cancer

Takayuki Oishi; Yuka Sasaki; Ying Tong; Lichao Chen; Takae Onodera; Satoru Iwasa; Emiko Udo; Bungo Furusato; Hiroaki Fujimori; Shoji Imamichi; Takuya Honda; Tadayoshi Bessho; Junya Fukuoka; Kazuto Ashizawa; Kazuyoshi Yanagihara; Kazuhiko Nakao; Yasuhide Yamada; Nobuyoshi Hiraoka; Mitsuko Masutani

doi:10.35772/ghm.2021.01001

Original Article

A newly established monoclonal antibody against ERCC1 detects major isoforms of ERCC1 in gastric cancer

Takayuki Oishi, Yuka Sasaki, Ying Tong, Lichao Chen, Takae Onodera, Satoru Iwasa, Emiko Udo, Bungo Furusato, Hiroaki Fujimori, Shoji Imamichi, Takuya Honda, Tadayoshi Bessho, Junya Fukuoka, Kazuto Ashizawa, Kazuyoshi Yanagihara, Kazuhiko Nakao, Yasuhide Yamada, Nobuyoshi Hiraoka, Mitsuko Masutani

Author information

Takayuki Oishi
Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Laboratory of Collaborative Research, Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.
Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Yuka Sasaki
Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Laboratory of Collaborative Research, Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.
Department of Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Ying Tong
Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Lichao Chen
Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Takae Onodera
Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Laboratory of Collaborative Research, Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.
Department of Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Satoru Iwasa
Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan;
Emiko Udo
Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan;
Cancer Genomics Unit, Clinical Genomics Center, Nagasaki University Hospital, Nagasaki, Japan;
Bungo Furusato
Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan;
Cancer Genomics Unit, Clinical Genomics Center, Nagasaki University Hospital, Nagasaki, Japan;
Hiroaki Fujimori
Department of Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Shoji Imamichi
Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Laboratory of Collaborative Research, Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.
Takuya Honda
Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Clinical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan;
Tadayoshi Bessho
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Junya Fukuoka
Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan;
Kazuto Ashizawa
Cancer Genomics Unit, Clinical Genomics Center, Nagasaki University Hospital, Nagasaki, Japan;
Department of Clinical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan;
Kazuyoshi Yanagihara
Division of Biomarker Discovery, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Tokyo, Japan.
Kazuhiko Nakao
Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Yasuhide Yamada
Department of Medical Oncology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Comprehensive Cancer Center, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.
Nobuyoshi Hiraoka
Division of Pathology, National Cancer Center Hospital, Tokyo, Japan.
Mitsuko Masutani
Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Laboratory of Collaborative Research, Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.
Department of Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Keywords: excision repair cross-complementing group 1, gastric tumor, cisplatin, predictive biomarker

JOURNAL FREE ACCESS

2021 Volume 3 Issue 4 Pages 226-235

DOI https://doi.org/10.35772/ghm.2021.01001

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Abstract

Identifying patients resistant to cisplatin treatment is expected to improve cisplatin-based chemotherapy for various types of cancers. Excision repair cross-complementing group 1 (ERCC1) is involved in several repair processes of cisplatin-induced DNA crosslinks. ERCC1 overexpression is reported as a candidate prognostic factor and considered to cause cisplatin resistance in major solid cancers. However, anti-ERCC1 antibodies capable of evaluating expression levels of ERCC1 in clinical specimens were not fully optimized. A mouse monoclonal antibody against human ERCC1 was generated in this study. The developed antibody 9D11 specifically detected isoforms of 201, 202, 203 but not 204, which lacks the exon 3 coding region. To evaluate the diagnostic usefulness of this antibody, we have focused on gastric cancer because it is one of the major cancers in Japan. When ERCC1 expression was analyzed in seventeen kinds of human gastric cancer cell lines, all the cell lines were found to express either 201, 202, and/or 203 as major isoforms of ERCC1, but not 204 by Western blotting analysis. Immunohistochemical staining showed that ERCC1 protein was exclusively detected in nuclei of the cells and a moderate level of constant positivity was observed in nuclei of vascular endothelial cells. It showed a clear staining pattern in clinical specimens of gastric cancers. Antibody 9D11 may thus be useful for estimating expression levels of ERCC1 in clinical specimens.

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