Overexpression of glypican-1 implicates poor prognosis and their chemoresistance in oesophageal squamous cell carcinoma

Hisashi Hara, Tsuyoshi Takahashi, Satoshi Serada, Minoru Fujimoto, Tomoharu Ohkawara, Rie Nakatsuka, Emi Harada, Takahiko Nishigaki, Yusuke Takahashi, Satoshi Nojima, Yasuhiro Miyazaki, Tomoki Makino, Yukinori Kurokawa, Makoto Yamasaki, Hiroshi Miyata, Kiyokazu Nakajima, Shuji Takiguchi, Eiichi Morii, Masaki Mori, Yuichiro DokiTetsuji Naka

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: Despite the recent improvements in multimodal therapies for oesophageal squamous cell carcinoma (ESCC), the prognosis remains poor. The identification of suitable biomarkers for predicting the prognosis and chemo-sensitivity is required to develop targeted treatments and improve treatment results. Methods: Proteins highly expressed in ESCC cell lines compared with normal oesophageal cell lines were screened by isobaric tag for relative and absolute quantitation (iTRAQ). We identified glypican-1 (GPC1) as a novel molecule. The clinicopathological characteristics of GPC1 were evaluated by immunohistochemistry using ESCC specimens, and clinical parameters were assessed. The correlation between GPC1 expression levels and chemo-sensitivity were analysed in vitro. Results: In the immunohistochemical assessment of 175 ESCC patients, 98.8% expressed GPC1. These patients demonstrated significantly poorer prognosis compared with patients with low-GPC1 expression by survival assay (P<0.001). Higher chemoresistance was observed in the GPC1 high-expression group. GPC1 expression levels positively correlated with chemo-sensitivity against cis-Diammineplatinum (II) dichloride (CDDP), and are potentially associated with anti-apoptotic function based on alterations in the MAPK downstream signalling pathway and Bcl-2 family member proteins. Conclusions: GPC1 is an independent prognostic factor in ESCC and is a critical molecule for altering the threshold of chemoresistance to CDDP.

Original languageEnglish
Pages (from-to)66-75
Number of pages10
JournalBritish journal of cancer
Volume115
Issue number1
DOIs
Publication statusPublished - Jun 28 2016

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Glypicans
Cell Line
Esophageal Squamous Cell Carcinoma
Proteins
Therapeutics
Biomarkers
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Hara, H., Takahashi, T., Serada, S., Fujimoto, M., Ohkawara, T., Nakatsuka, R., ... Naka, T. (2016). Overexpression of glypican-1 implicates poor prognosis and their chemoresistance in oesophageal squamous cell carcinoma. British journal of cancer, 115(1), 66-75. https://doi.org/10.1038/bjc.2016.183

Overexpression of glypican-1 implicates poor prognosis and their chemoresistance in oesophageal squamous cell carcinoma. / Hara, Hisashi; Takahashi, Tsuyoshi; Serada, Satoshi; Fujimoto, Minoru; Ohkawara, Tomoharu; Nakatsuka, Rie; Harada, Emi; Nishigaki, Takahiko; Takahashi, Yusuke; Nojima, Satoshi; Miyazaki, Yasuhiro; Makino, Tomoki; Kurokawa, Yukinori; Yamasaki, Makoto; Miyata, Hiroshi; Nakajima, Kiyokazu; Takiguchi, Shuji; Morii, Eiichi; Mori, Masaki; Doki, Yuichiro; Naka, Tetsuji.

In: British journal of cancer, Vol. 115, No. 1, 28.06.2016, p. 66-75.

Research output: Contribution to journalArticle

Hara, H, Takahashi, T, Serada, S, Fujimoto, M, Ohkawara, T, Nakatsuka, R, Harada, E, Nishigaki, T, Takahashi, Y, Nojima, S, Miyazaki, Y, Makino, T, Kurokawa, Y, Yamasaki, M, Miyata, H, Nakajima, K, Takiguchi, S, Morii, E, Mori, M, Doki, Y & Naka, T 2016, 'Overexpression of glypican-1 implicates poor prognosis and their chemoresistance in oesophageal squamous cell carcinoma', British journal of cancer, vol. 115, no. 1, pp. 66-75. https://doi.org/10.1038/bjc.2016.183
Hara, Hisashi ; Takahashi, Tsuyoshi ; Serada, Satoshi ; Fujimoto, Minoru ; Ohkawara, Tomoharu ; Nakatsuka, Rie ; Harada, Emi ; Nishigaki, Takahiko ; Takahashi, Yusuke ; Nojima, Satoshi ; Miyazaki, Yasuhiro ; Makino, Tomoki ; Kurokawa, Yukinori ; Yamasaki, Makoto ; Miyata, Hiroshi ; Nakajima, Kiyokazu ; Takiguchi, Shuji ; Morii, Eiichi ; Mori, Masaki ; Doki, Yuichiro ; Naka, Tetsuji. / Overexpression of glypican-1 implicates poor prognosis and their chemoresistance in oesophageal squamous cell carcinoma. In: British journal of cancer. 2016 ; Vol. 115, No. 1. pp. 66-75.
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AU - Hara, Hisashi

AU - Takahashi, Tsuyoshi

AU - Serada, Satoshi

AU - Fujimoto, Minoru

AU - Ohkawara, Tomoharu

AU - Nakatsuka, Rie

AU - Harada, Emi

AU - Nishigaki, Takahiko

AU - Takahashi, Yusuke

AU - Nojima, Satoshi

AU - Miyazaki, Yasuhiro

AU - Makino, Tomoki

AU - Kurokawa, Yukinori

AU - Yamasaki, Makoto

AU - Miyata, Hiroshi

AU - Nakajima, Kiyokazu

AU - Takiguchi, Shuji

AU - Morii, Eiichi

AU - Mori, Masaki

AU - Doki, Yuichiro

AU - Naka, Tetsuji

PY - 2016/6/28

Y1 - 2016/6/28

N2 - Background: Despite the recent improvements in multimodal therapies for oesophageal squamous cell carcinoma (ESCC), the prognosis remains poor. The identification of suitable biomarkers for predicting the prognosis and chemo-sensitivity is required to develop targeted treatments and improve treatment results. Methods: Proteins highly expressed in ESCC cell lines compared with normal oesophageal cell lines were screened by isobaric tag for relative and absolute quantitation (iTRAQ). We identified glypican-1 (GPC1) as a novel molecule. The clinicopathological characteristics of GPC1 were evaluated by immunohistochemistry using ESCC specimens, and clinical parameters were assessed. The correlation between GPC1 expression levels and chemo-sensitivity were analysed in vitro. Results: In the immunohistochemical assessment of 175 ESCC patients, 98.8% expressed GPC1. These patients demonstrated significantly poorer prognosis compared with patients with low-GPC1 expression by survival assay (P<0.001). Higher chemoresistance was observed in the GPC1 high-expression group. GPC1 expression levels positively correlated with chemo-sensitivity against cis-Diammineplatinum (II) dichloride (CDDP), and are potentially associated with anti-apoptotic function based on alterations in the MAPK downstream signalling pathway and Bcl-2 family member proteins. Conclusions: GPC1 is an independent prognostic factor in ESCC and is a critical molecule for altering the threshold of chemoresistance to CDDP.

AB - Background: Despite the recent improvements in multimodal therapies for oesophageal squamous cell carcinoma (ESCC), the prognosis remains poor. The identification of suitable biomarkers for predicting the prognosis and chemo-sensitivity is required to develop targeted treatments and improve treatment results. Methods: Proteins highly expressed in ESCC cell lines compared with normal oesophageal cell lines were screened by isobaric tag for relative and absolute quantitation (iTRAQ). We identified glypican-1 (GPC1) as a novel molecule. The clinicopathological characteristics of GPC1 were evaluated by immunohistochemistry using ESCC specimens, and clinical parameters were assessed. The correlation between GPC1 expression levels and chemo-sensitivity were analysed in vitro. Results: In the immunohistochemical assessment of 175 ESCC patients, 98.8% expressed GPC1. These patients demonstrated significantly poorer prognosis compared with patients with low-GPC1 expression by survival assay (P<0.001). Higher chemoresistance was observed in the GPC1 high-expression group. GPC1 expression levels positively correlated with chemo-sensitivity against cis-Diammineplatinum (II) dichloride (CDDP), and are potentially associated with anti-apoptotic function based on alterations in the MAPK downstream signalling pathway and Bcl-2 family member proteins. Conclusions: GPC1 is an independent prognostic factor in ESCC and is a critical molecule for altering the threshold of chemoresistance to CDDP.

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