High expression of heat shock protein 90 is associated with tumor aggressiveness and poor prognosis in patients with advanced gastric cancer.
High expression of heat shock protein 90 is associated with tumor aggressiveness and poor prognosis in patients with advanced gastric cancer.
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DOI：
10.1371/journal.pone.0062876
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tang H
中科院分区：
文献类型：
--
作者：
Wang J;Cui S;Zhang X;Wu Y;Tang H
热休克蛋白90（HSP 90）在许多恶性肿瘤中过度表达，与预后不良密切相关。然而，HSP 90在胃癌中的作用尚未完全阐明。本研究旨在探讨HSP 90在进展期胃癌中的表达与临床病理参数及预后的关系，以及新辅助化疗后HSP 90表达的变化。应用免疫组织化学方法检测322例进展期胃癌组织中HSP 90和基质金属肽酶9（MMP-9）的表达。分析HSP 90与临床病理参数及预后的关系。对54例接受1-2周期新辅助化疗的患者进行热休克蛋白90（HSP 90）水平与化疗效果的关系评价。322例进展期胃癌组织中HSP 90阳性表达率为69.6%。HSP 90蛋白表达与胃癌浸润深度、淋巴结转移及临床分期有关（P <0.001）。HSP 90阳性表达率在肿瘤浸润明显组（P<0.001）和淋巴结转移组（P<0.001）中均明显增高。322例胃癌组织中HSP 90与MMP-9的表达呈显著相关（P<0.001）。在单因素和多因素分析中，HSP 90是无复发生存期（RFS）和总生存期（OS）的独立预后因素。提示HSP 90在肿瘤的侵袭、转移及预后中起重要作用，有望成为预测肿瘤预后的新靶点。
The heat shock protein 90 (HSP90) is overexpressed and highly associated with poor prognosis in many malignancies. However, the role of HSP90 in gastric cancer has not been thoroughly elucidated. The aim of this study is to investigate the relationship of HSP90 expression with clinicopathological parameters and prognosis in advanced gastric cancer, and estimate the alteration of HSP90 expression after neoadjuvant chemotherapy. HSP90 and matrix metallopeptidase 9 (MMP-9) antigen expression was evaluated by immunohistochemistry in 322 advanced gastric carcinoma samples. The relationships between HSP90 and clinicopathological parameters and prognosis were analyzed. The response of HSP90 level was assessed in chemotherapeutic effect in 54 patients received 1–2 cycles of neoadjuvant chemotherapy. The positive expression of HSP90 was found to be 69.6% in 322 advanced gastric carcinoma samples. HSP90 protein expression was significantly associated with depth invasion (P<0.001), lymph node metastasis (P<0.001) and stage of disease (P<0.001). The positive rates of HSP90 expression were higher in both prominent serosal invasion group (P<0.001) and lymph node metastasis group (P<0.001). Moreover, HSP90 was significantly correlated with MMP-9 among 322 gastric cancer tissues (P<0.001). In univariate and multivariate analyses, HSP90 was an independent prognostic factor for both recurrence-free survival (RFS) and overall survival (OS). These results suggested that HSP90 may play an important role on tumor invasion, metastasis and prognosis, and might act as a promising target for prognostic prediction.
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