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

被引:33
作者
Feng, Juan [1 ]
Xie, Guiyuan [2 ]
Zhan, Yuting [1 ]
Lu, Junmi [1 ]
Xu, Lina [1 ]
Fan, Songqing [1 ]
Wang, Weiyuan [1 ]
机构
[1] Cent S Univ, Xiangya Hosp 2, Dept Pathol, Changsha 410011, Hunan, Peoples R China
[2] Cent S Univ, Xiangya Hosp 2, Dept Oncol, Changsha, Hunan, Peoples R China
关键词
HIF-1; alpha; HSP90; nasopharyngeal carcinoma; p-AKT; prognosis; HYPOXIA; FACTOR-1; PROTEIN; HSP90-ALPHA; DEGRADATION; RECRUITMENT; INHIBITION; APOPTOSIS; BINDING;
D O I
10.1111/his.13862
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Aims HSP90, as a molecular chaperone, has numerous substrate proteins, including HIF-1 alpha and p-AKT, but the relationships among HSP90, HIF-1 alpha and p-AKT have not been investigated in NPC. We examined and analysed the correlation between expression of HSP90, HIF-1 alpha 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-1 alpha and p-AKT proteins in these tissues by immunohistochemistry. Results The results indicated that overexpression of HSP90, HIF-1 alpha and p-AKT in NPC was significantly higher than that in non-cancerous nasopharyngeal epithelia (P < 0.05). The overexpression of HIF-1 alpha 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-1 alpha (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-1 alpha expression (r = 0.367, P < 0.001) and p-AKT (r = 0.142, P = 0.003) expression in NPC. Furthermore, HIF-1 alpha 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-1 alpha (P = 0.036) and increased p-AKT (P = 0.044). Multivariate Cox regression analysis further identified that HSP90 and HIF-1 alpha were independent poor prognostic factors for NPC. Conclusions Taken together, elevated HSP90 was associated with expression of HIF-1 alpha and p-AKT in NPC. Furthermore, high expression of HSP90 and HIF-1 alpha could be used as a novel independent poor prognostic biomarker for patients with NPC.
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页码:202 / 212
页数:11
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