HSP90 水平升高与 HIF-1α 和 p-AKT 的表达相关，可预测鼻咽癌的不良预后。

Elevated HSP90 associates with expression of HIF-1α and p-AKT and is predictive of poor prognosis in nasopharyngeal carcinoma.

机构信息

Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

出版信息

Histopathology. 2019 Aug;75(2):202-212. doi: 10.1111/his.13862. Epub 2019 Jun 17.

DOI:10.1111/his.13862

PMID:30882922

Abstract

AIMS

HSP90, as a molecular chaperone, has numerous substrate proteins, including HIF-1α and p-AKT, but the relationships among HSP90, HIF-1α and p-AKT have not been investigated in NPC. We examined and analysed the correlation between expression of HSP90, HIF-1α and p-AKT and clinicopathological features of NPC.

METHODS

We collected 445 cases of NPC and 54 cases of non-cancerous nasopharyngeal epithelia tissues, detected expression of HSP90, HIF-1α and p-AKT proteins in these tissues by immunohistochemistry.

RESULTS

The results indicated that overexpression of HSP90, HIF-1α and p-AKT in NPC was significantly higher than that in non-cancerous nasopharyngeal epithelia (P < 0.05). The overexpression of HIF-1α in primary NPC was significantly lower than that in matched lymph node metastatic NPC (P = 0.024) or recurrent NPC (P = 0.039). The overexpression of HSP90 (P < 0.001) and HIF-1α (P = 0.031) was evidently higher in late stage NPC. NPC patients with lymph node metastasis (LNM) had a higher overexpression rate of HSP90 (P < 0.001) than those without LNM. Increased HSP90 expression was positively associated with HIF-1α expression (r = 0.367, P < 0.001) and p-AKT (r = 0.142, P = 0.003) expression in NPC. Furthermore, HIF-1α was also related to p-AKT expression (r = 0.114, P = 0.017). The overall survival rate for NPC patients with up-regulated HSP90 was significantly lower than those with down-regulated HSP90 (P < 0.001), as was found with raised HIF-1α (P = 0.036) and increased p-AKT (P = 0.044). Multivariate Cox regression analysis further identified that HSP90 and HIF-1α were independent poor prognostic factors for NPC.

CONCLUSIONS

Taken together, elevated HSP90 was associated with expression of HIF-1α and p-AKT in NPC. Furthermore, high expression of HSP90 and HIF-1α could be used as a novel independent poor prognostic biomarker for patients with NPC.

摘要

目的

HSP90 作为一种分子伴侣，有许多底物蛋白，包括 HIF-1α 和 p-AKT，但 HSP90、HIF-1α 和 p-AKT 之间的关系尚未在 NPC 中进行研究。我们检查和分析了 HSP90、HIF-1α 和 p-AKT 的表达与 NPC 的临床病理特征之间的相关性。

方法

我们收集了 445 例 NPC 和 54 例非癌性鼻咽上皮组织，通过免疫组织化学检测这些组织中 HSP90、HIF-1α 和 p-AKT 蛋白的表达。

结果

结果表明，HSP90、HIF-1α 和 p-AKT 在 NPC 中的过度表达明显高于非癌性鼻咽上皮（P<0.05）。原发 NPC 中 HIF-1α 的过度表达明显低于匹配的淋巴结转移性 NPC（P=0.024）或复发性 NPC（P=0.039）。晚期 NPC 中 HSP90（P<0.001）和 HIF-1α（P=0.031）的过度表达明显更高。有淋巴结转移（LNM）的 NPC 患者 HSP90（P<0.001）的过度表达率明显高于无 LNM 的患者。在 NPC 中，HSP90 的表达增加与 HIF-1α 的表达呈正相关（r=0.367，P<0.001）和 p-AKT（r=0.142，P=0.003）的表达。此外，HIF-1α 也与 p-AKT 的表达相关（r=0.114，P=0.017）。HSP90 上调的 NPC 患者的总生存率明显低于 HSP90 下调的患者（P<0.001），HIF-1α 上调（P=0.036）和 p-AKT 上调（P=0.044）的患者也是如此。多变量 Cox 回归分析进一步确定 HSP90 和 HIF-1α 是 NPC 的独立不良预后因素。