Abstract
Nasopharyngeal carcinoma (NPC) is a malignant tumor of the head and neck region, which frequently occurs in Southeast Asia, especially in the south of China. It is known that the mammalian target of rapamycin (mTOR) pathway plays a central role in regulating cellular functions, including proliferation, growth, survival, mobility, and angiogenesis. Aberrant expression of the mTOR signaling pathway molecules has been found in many types of cancer. However, whether the alterations of p-Akt, p-p70S6K and p-4EBP1 protein expression are associated with clinicopathological features and prognostic implications in NPC have not been reported. The purposes of the present study are to investigate the association between the expression of p-Akt, p-p70S6K and p-4EBP1 proteins and clinicopathological features in NPC by immunohistochemistry. The results showed that the positive percentage of p-Akt, p-p70S6K and p-4EBP1 proteins expression in NPC (47.2%, 73.0% and 61.7%, respectively) was significantly higher than that in the non-cancerous nasopharyngeal control tissue (33.3%, 59.1% and 47.0%, respectively). There was a significantly higher positive expression of p-Akt in undifferentiated non-keratinizing nasopharyngeal carcinoma than that in differentiated non-keratinizing nasopharyngeal carcinoma (P = 0.014). Additionally, positive expression of p-p70S6K and p-4EBP1 proteins, and positive expression of either of p-Akt, p-p70S6K and p-4EBP1 were significantly correlated inversely with overall survival rates of NPC patients (P = 0.023, P = 0.033, P = 0.008, respectively). Spearman’s rank correlation test showed that expression of p-Akt in NPC was significantly associated with expression of p-p70S6K (r = 0.263, P<0.001) and p-4EBP1(r = 0.284, P<0.001). Also there was an obviously positive association between expression of p-p70S6K and p-4EBP1 proteins in NPC (r = 0.286, P<0.001). Multivariate Cox regression analysis further identified positive expression of p-4EBP1 and p-p70S6K proteins were the independent poor prognostic factors for NPC (P = 0.043, P = 0.027, respectively). Taken together, high expression of p-p70S6K and p-4EBP1 proteins may act as valuable independent biomarkers to predict a poor prognosis of NPC.
Highlights
Nasopharyngeal carcinoma (NPC) is a kind of head and neck malignant tumor, which frequently occurs in Southeast Asia, especially in the south of China [1]
It appears that multiple factors are involved in the carcinogenesis of NPC ranging from EpsteinBarr virus (EBV) infection, environmental factors and genetic susceptibility, to the aberrant expression of oncogenes/tumorsuppressor genes and the abnormal activation of signaling pathways such as Akt/mammalian target of rapamycin (mTOR) pathway, mitogen-activated protein kinases and Wnt signaling pathway [1,2]
We further investigated the associations between the expression of p-Akt, p-4EBP1 and p-p70S6K proteins and clinicopathological features of NPC including age, gender, histological type, clinical stage, lymph node metastasis status and survival status in univariate chi-square test
Summary
Nasopharyngeal carcinoma (NPC) is a kind of head and neck malignant tumor, which frequently occurs in Southeast Asia, especially in the south of China [1]. It appears that multiple factors are involved in the carcinogenesis of NPC ranging from EpsteinBarr virus (EBV) infection, environmental factors and genetic susceptibility, to the aberrant expression of oncogenes/tumorsuppressor genes and the abnormal activation of signaling pathways such as Akt/mTOR pathway, mitogen-activated protein kinases and Wnt signaling pathway [1,2]. A serine–threonine kinase, plays a central role in the PI3K/ Akt/mTOR signaling pathway. Whether expression of p-Akt, p-p70S6K and p-4EBP1 proteins is associated with clinicopathological features and prognostic implications in NPC has not been reported
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