Overexpression of glypican-1 implicates poor prognosis and their chemoresistance in oesophageal squamous cell carcinoma.
Overexpression of glypican-1 implicates poor prognosis and their chemoresistance in oesophageal squamous cell carcinoma.
复制标题
磷脂酰肌醇蛋白聚糖-1过表达与食管鳞癌预后不良及化疗耐药有关。
DOI：
10.1038/bjc.2016.183
复制
发表时间：
2016-06-28
影响因子：
8.8
通讯作者：
Naka T
中科院分区：
文献类型：
--
作者：
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
尽管最近食管鳞状细胞癌（ESCC）的多模式治疗有所改善，但预后仍然很差。需要鉴定用于预测预后和化学敏感性的合适的生物标志物以开发靶向治疗并改善治疗结果。采用同量异位素标签法（iTRAQ）对食管癌细胞系中相对于正常食管癌细胞系高表达的蛋白质进行相对和绝对定量分析。我们发现磷脂酰肌醇蛋白聚糖-1（GPC 1）是一种新的分子。采用免疫组化方法对GPC 1的临床病理特征进行评价，并对临床参数进行评估。分析GPC 1表达水平与体外化疗敏感性的相关性。在175例ESCC患者的免疫组化评估中，98.8%表达GPC 1。生存分析显示，与GPC 1低表达的患者相比，这些患者的预后明显较差（P<0.001）。GPC 1高表达组化疗耐药性明显升高。GPC 1表达水平与对顺式二氯二氨铂（II）（CDDP）的化学敏感性呈正相关，并且可能与基于MAPK下游信号通路和Bcl-2家族成员蛋白的改变的抗凋亡功能相关。GPC 1是ESCC的独立预后因子，是改变CDDP耐药阈值的关键分子。
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.