Increased expression of Cks1 protein is associated with lymph node metastasis and poor prognosis in nasopharyngeal carcinoma

Diagnostic pathology(2017)

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摘要
Background The Cks1 protein is an essential factor in regulating cell cycle by mediating the ubiquitination of CDK inhibitor p27 kip1 . It has been reported that aberrant expression of Cks1 and p27 kip1 proteins was found in various tumors and related to initiation and progression of carcinomas. However, the potential roles which Cks1 and p27 KIP1 proteins play in NPC remain unclear. This study aims to examine the expression status of Cks1 and p27 kip1 and their possible prognostic significance in NPC. Methods Paraffin-embedded specimens with NPC ( n = 168) and non-tumor nasopharyngeal tissues ( n = 49) were analyzed by IHC. Results Expression of Cks1 increased in NPC tissues compared with non-tumor nasopharyngeal tissues ( P < 0.05), whereas p27 kip1 protein frequently expressed in non-tumor nasopharyngeal tissues compared with NPC tissues ( P < 0.05). There was a significant reverse correlation between Cks1 and p27 kip1 protein expression in NPC ( r = −0.189, P < 0.05).In addition, Kaplan-Meier survival curve showed that there was a significant tendency of shorter overall survival (OS) in NPC patients with Cks1 positive expression compared to negative ones, especially in patients with lymph node metastasis ( P < 0.001, respectively). But there was no significance between p27 kip1 expression and survival viability of NPC patients. Multivariate Cox regression analysis further identified increased expression of Cks1 was the independent poor prognostic factor for NPC ( p = 0.13). Conclusion Our research found expression of Cks1 increased and was inverse to the expression of p27 KIP1 . High expression of Cks1 was significantly associated with lymph node metastasis and survival status in NPC. In addition, the abnormally high level of Cks1 protein was proved to be an independent poor prognostic factor in NPC. These results may provide novel clue for NPC therapy method.
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关键词
Cyclin-dependent protein kinase regulatory subunit 1 (CKS1),Lymph node metastasis (LNM),Nasopharyngeal carcinoma (NPC),Prognostic factor
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