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

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.

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

“…250,251 In a study of NPC epithelial tissue, high expression of HIF-1α is found to be a new independent biomarker for predicting poor prognosis in NPC patients. 252 It is found that the serum BMI-1 antibody in patients is significantly higher than in normal persons, suggesting that BMI-1 antibody may be a potential biomarker of NPC and has diagnostic and prognostic value. 253 CDH6 is overexpressed in the LMP1-positive NPC tissues, which can promote EMT and metastasis of NPC, which may be a therapeutic target of NPC.…”

<p>Increased expression of heat shock protein (HSP) 10 and HSP70 correlates with poor prognosis of nasopharyngeal carcinoma</p>

“…Our previous study has demonstrated that elevated expression of HSP10 protein inhibits apoptosis and associates with poor prognosis of astrocytoma, high expression of heat shock protein 10 correlates negatively with estrogen/progesterone receptor status and predicts poor prognosis in invasive ductal breast carcinoma, and high expression of HSP10 is associated with poor prognosis in oral squamous cell carcinoma 23–25. We also found that high expression of HSP90 could be used as a novel independent poor prognostic biomarker for patients with NPC 26. So far, the correlation between expression of HSP10 and HSP70 proteins and clinicopathological characteristics of NPC has not been reported.…”

“…The IHC staining for HSP10 and HSP70 in NPC samples was carried out using ready-to-use Envision TM + Dual Link System-HRP methods (Dako, Carpinteria, CA, USA). According to our laboratory experience,23–26 the staining conditions for each antibody were adjusted. In brief, each section was deparaffinized and rehydrated, and high-temperature antigen retrieval was achieved for all antibodies by heating the samples in 0.01 M citrate buffer in a domestic microwave oven at full power (750 W) for 15 mins.…”

Overexpression of p-Akt, p-mTOR and p-eIF4E proteins associates with metastasis and unfavorable prognosis in non-small cell lung cancer

“…Positive expression of p-Akt and any positive of p-Akt/p-mTOR/ p-eIF4E were statistically higher than those in the never-smoker patients. Moreover, positive expression of p-Akt protein was more frequent in advanced NSCLC patients, while p-Akt protein was not higher in advanced stage of NPC and esophageal squamous cell carcinoma (ESCC) [32][33]. Also, NSCLC patients with positive expression of p-Akt proteins tend to have LNM and lower overall survival rates.…”