Glucose-regulated protein 58 modulates cell invasiveness and serves as a prognostic marker for cervical cancer
Glucose-regulated protein 58 modulates cell invasiveness and serves as a prognostic marker for cervical cancer
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DOI：
10.1111/j.1349-7006.2011.02102.x
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发表时间：
2011-12-01
期刊：
影响因子：
5.7
通讯作者：
Lin, Kwang-Huei
中科院分区：
文献类型：
--
作者：
Liao, Chia-Jung;Wu, Tzu-I;Lin, Kwang-Huei
人乳头瘤病毒感染是关键，但不足以导致宫颈癌。宫颈癌发生的分子标志物是必不可少的。本研究的目的是鉴定宫颈癌中异常表达的蛋白质，并确定其临床意义。双向聚丙烯酰胺凝胶电泳（2-DE）蛋白质组学策略用于筛选候选蛋白。免疫印迹和免疫组化（IHC）分析证实2-DE的结果，并评估其临床意义。葡萄糖调节蛋白58（Grp 58）在73%的癌症中过表达。免疫组化染色结果显示，腺癌组织中Grp 58的表达明显高于鳞癌组织（P < 0.05）。Grp 58染色在AD中是强烈的，渗透深度大于宫颈基质的一半（P = 0.033）。Grp 58高表达与低总生存率和无复发生存率（RFS）相关（分别为P = 0.007和P = 0.013）。多因素分析显示Grp 58高表达（P = 0.042）和淋巴结转移（P = 0.026）是RFS的独立预后因素。同时表现出Grp 58高表达和淋巴结转移的患者显示出比其他患者组更差的结果。在功能研究中，在异种移植小鼠模型中，HeLa细胞中Grp 58的敲低导致细胞侵袭性降低和肺转移抑制。总之，Grp 58是宫颈AD的一个有效的预后因子。Grp 58指数与颈淋巴结转移情况的联合检测有助于预测颈AD的预后。（Cancer Sci 2011; 102：22552263）
Human papilloma virus infection is critical but not sufficient to cause cervical cancer. Molecular markers of cervical carcinogenesis are essential. The aim of this study was to identify aberrantly expressed proteins in cervical cancer and determine their clinical significance. A two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomic strategy was used for screening candidate proteins. Immunoblotting and immunohistochemical (IHC) analyses were performed to confirm the results of 2-DE, and the clinical significance was estimated. Glucose-regulated protein 58 (Grp58) was overexpressed in 73% of cancers. The IHC staining showed that the Grp58 histoscore was significantly higher in patients with adenocarcinoma (AD) compared with squamous cell carcinoma (P < 0.05). Grp58 staining was intense in AD with a penetration depth greater than half of the cervical stroma (P = 0.033). High Grp58 expression was associated with low overall survival and recurrence-free survival (RFS) rates (P = 0.007 and P = 0.013, respectively). In multivariate analysis, high Grp58 expression (P = 0.042) and lymph node metastasis (P = 0.026) were determined as independent prognostic factors for RFS. Patients exhibiting both high Grp58 expression and lymph node metastasis displayed poorer outcomes than the other patient groups. In functional studies, knockdown of Grp58 in HeLa cells led to decreased cell invasiveness and inhibition of lung metastasis in a xenograft mouse model. In conclusion, Grp58 serves as a potent prognostic factor of cervical AD. Estimation of the Grp58 index in conjunction with the lymph node metastasis status might aid in predicting the prognosis of cervical AD. (Cancer Sci 2011; 102: 22552263)