Abstract
BackgroundThe Cks1 protein is an essential factor in regulating cell cycle by mediating the ubiquitination of CDK inhibitor p27kip1. It has been reported that aberrant expression of Cks1 and p27kip1 proteins was found in various tumors and related to initiation and progression of carcinomas. However, the potential roles which Cks1 and p27KIP1 proteins play in NPC remain unclear. This study aims to examine the expression status of Cks1 and p27kip1 and their possible prognostic significance in NPC.MethodsParaffin-embedded specimens with NPC (n = 168) and non-tumor nasopharyngeal tissues (n = 49) were analyzed by IHC.ResultsExpression of Cks1 increased in NPC tissues compared with non-tumor nasopharyngeal tissues (P < 0.05), whereas p27kip1 protein frequently expressed in non-tumor nasopharyngeal tissues compared with NPC tissues (P < 0.05). There was a significant reverse correlation between Cks1 and p27kip1 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 p27kip1 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).ConclusionOur research found expression of Cks1 increased and was inverse to the expression of p27KIP1. 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.
Highlights
The cyclin–dependent protein kinase regulatory subunit 1 (Cks1) protein is an essential factor in regulating cell cycle by mediating the ubiquitination of Cyclin-dependent kinase (CDK) inhibitor p27kip1
Expression of Cks1 protein increased and p27kip1 protein decreased in Nasopharyngeal carcinoma (NPC) To clarify the significance of Cks1 and p27kip1 proteins in NPC, we investigated the expression of Cks1 and p27kip1 in NPC and non-tumor nasopharyngeal tissues by IHC method
We found that the expression of Cks1 increased in NPC tissue, and high expression of Cks1 protein was correlated with Lymph node metastasis (LNM) status and survival status in NPC patients
Summary
The Cks protein is an essential factor in regulating cell cycle by mediating the ubiquitination of CDK inhibitor p27kip. It has been reported that aberrant expression of Cks and p27kip proteins was found in various tumors and related to initiation and progression of carcinomas. The potential roles which Cks and p27KIP1 proteins play in NPC remain unclear. This study aims to examine the expression status of Cks and p27kip and their possible prognostic significance in NPC. The initiation and progression of NPC involves various factors, including Epstein-Barr virus (EBV) infection, genetic susceptibility, exposure to chemical carcinogens and mutant expression of tumor-suppressor genes, etc [4, 5]. Essential biomarkers involved in critical genetic events that contribute to the carcinogenesis of NPC have been increasingly found.
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