Proteomic profiling of hepatocellular carcinoma in Chinese cohort reveals heat-shock proteins (Hsp27, Hsp70, GRP78) up-regulation and their associated prognostic values
Proteomic profiling of hepatocellular carcinoma in Chinese cohort reveals heat-shock proteins (Hsp27, Hsp70, GRP78) up-regulation and their associated prognostic values
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DOI：
10.1002/pmic.200500306
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发表时间：
2006-02-01
期刊：
影响因子：
3.4
通讯作者：
Fan, ST
中科院分区：
文献类型：
--
作者：
Luk, JM;Lam, CT;Fan, ST
为了方便鉴定与肝细胞癌（HCC）发病机制相关的候选分子生物标志物，我们通过2-DE研究了146个组织标本的蛋白表达谱，其中包括67对从HCC患者切除的肿瘤和邻近非肿瘤以及12个正常肝脏。在肝脏蛋白质组显示的1800个斑点中，三组之间共有90种蛋白质存在显著差异（P < 0.05）。通过MS/MS分析，在HCC中上调的3个候选标志物均具有高受试者工作特征（ROC）曲线，属于伴侣成员：热休克蛋白（Hsp）27、Hsp70和葡萄糖调节蛋白（GRP）78。Western blotting和免疫组织化学证实了这些伴侣蛋白在HCC组织中的过表达。与临床病理参数相关，Hsp27表达与x-胎蛋白水平相关（P = 0.007）， GRP78表达上调与肿瘤静脉浸润相关（P = 0.035）。没有观察到Hsp70与任何病理特征的显著关联。目前的HCC蛋白质组学分析显示，在应激性癌微环境下，肿瘤细胞努力增加具有细胞保护功能的伴侣蛋白的表达，促进肿瘤的生长和转移。
To facilitate the identification of candidate molecular biomarkers that are linked to the pathogenesis of hepatocellular carcinoma (HCC), we investigated protein-expression profiles of 146 tissue specimens including 67 pairs of tumors and adjacent non-tumors resected from HCC patients as well as 12 normal livers by 2-DE. Among the 1800 spots displayed in the liver proteome, a total of 90 protein species were found to be significantly different between the three groups (P < 0.05). Three of the top candidate markers up-regulated in HCC, with high receiver operating characteristic (ROC) curves, were identified by MS/MS analysis and belonged to the chaperone members: heat-shock protein (Hsp)27, Hsp70 and glucose-regulated protein (GRP)78. Over-expression of these chaperone proteins in HCC tissues was confirmed by Western blotting and immunohistochemistry. In correlation with clinico-pathological parameters, expression of Hsp27 was linked to (x-fetoprotein level (P = 0.007) whereas up-regulation of GRP78 was associated with tumor venous infiltration (P = 0.035). No significant association of Hsp70 with any pathologic features was observed. The present HCC proteome analysis revealed that in response to the stressful cancerous microenvironment, tumor cells strived to increase the expression of chaperone proteins for cyto-protective function and to enhance tumor growth and metastasis.