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

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13000-016-0589-9) contains supplementary material, which is available to authorized users.

Downregulation of CKS1B restrains the proliferation, migration, invasion and angiogenesis of retinoblastoma cells through the MEK/ERK signaling pathway

“…Cyclin-dependent kinase regulatory subunit 1B (CKS1B) is a member of the Cks/Suc1 family of small proteins (9-18 kDa) that bind the catalytic subunit of cyclin-dependent protein kinases and regulate their function (9). Elevated expression of CKS1B has been associated with increased p27 (Kip1) turnover and cell proliferation, and poor prognosis in numerous tumor types, including oral, gastric, breast and colon carcinoma (10). Overexpression of CKS1B also activates the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway (11).…”

Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis

“…Nevertheless, its relevance for hepato-and/or cholangiocarcinogenesis is yet to be unveiled. Additionally, CKS1B represents an oncogene that has been reported increased in retinoblastoma, HCC, nasopharyngeal carcinoma and multiple myeloma [63][64][65][66][67]. Importantly, CKS1B upregulation has been positively related to increased proliferation, migration, angiogenesis, invasion and chemoresistance, being further related with lymph node metastasis and worse prognosis.…”

Prognostic and clinicopathological significance of Cks1 in cancer: Evidence from a meta‐analysis

“…and data. Finally, 19 studies (Bochis et al, 2017;Brożyna et al, 2018;Kawakami et al, 2007;Kitajima et al, 2004;Lee et al, 2013;Li et al, 2007;Liu et al, 2008;Masuda et al, 2003;Miyai et Xu et al, 2017;Zolota et al, 2010) were identified with a total of 2,224 patients in this metaanalysis ( Figure 1). The sample size for the enrolled studies ranged from 30 to 482 patients and the mean sample size was 117.1 patients.…”