TY - JOUR
T1 - Overexpression of glypican-1 implicates poor prognosis and their chemoresistance in oesophageal squamous cell carcinoma
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
N1 - Publisher Copyright:
© 2016 Cancer Research UK.
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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U2 - 10.1038/bjc.2016.183
DO - 10.1038/bjc.2016.183
M3 - Article
C2 - 27310703
AN - SCOPUS:84975106442
SN - 0007-0920
VL - 115
SP - 66
EP - 75
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 1
ER -
