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
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
Br J Cancer. 2016 Jun 28;115(1):66-75. doi: 10.1038/bjc.2016.183. Epub 2016 Jun 16.
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.
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.
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.
GPC1 is an independent prognostic factor in ESCC and is a critical molecule for altering the threshold of chemoresistance to CDDP.
尽管最近食管鳞状细胞癌（ESCC）的多模态治疗有所改善，但预后仍然很差。需要鉴定合适的生物标志物来预测预后和化疗敏感性，以开发靶向治疗并改善治疗效果。
通过相对与绝对定量的等压标记（iTRAQ）筛选与正常食管细胞系相比在ESCC细胞系中高表达的蛋白质。我们鉴定出磷脂酰肌醇蛋白聚糖-1（GPC1）为一种新分子。使用ESCC标本通过免疫组织化学评估GPC1的临床病理特征，并评估临床参数。在体外分析GPC1表达水平与化疗敏感性之间的相关性。
在对175例ESCC患者的免疫组织化学评估中，98.8%的患者表达GPC1。通过生存分析，这些患者的预后明显比低GPC1表达的患者差（P<0.001）。在GPC1高表达组中观察到更高的化疗耐药性。GPC1表达水平与对顺二氯二氨铂（CDDP）的化疗敏感性呈正相关，并且基于丝裂原活化蛋白激酶（MAPK）下游信号通路和Bcl-2家族成员蛋白的改变，可能与抗凋亡功能有关。
GPC1是ESCC的独立预后因素，并且是改变对CDDP化疗耐药阈值的关键分子。
