Clinicopathological and biological significance of CDC28 protein kinase regulatory subunit 2 overexpression in human gastric cancer

Abstract

Abstract. CDC28 protein kinase regulatory subunit 2 (CKS2)is a cyclin-dependent kinase subunit (cKS) family member that participates in cell cycle regulation. Few studies have investigated its involvement in gastric cancer. In this study, we focused on the clinical and biological significance of CKS2 overexpression in gastric cancer. The expression of CKS2 mRNA was studied by real-time quantitative reverse transcription polymerase chain reaction, and the expression status in each tumor was examined to varify whether any correlation existed with clinical and pathological factors. In addition, an immunohistochemical study was performed in selected samples. Moreover, we examined the impact of CKS2-siRNA in a gastric cancer cell line. A significantly higher expression of CKS2 mRNA was found in tumor tissues compared to paired normal tissues (p<0.01). Immunohistochemical analyses led to similar results. The overall five-year survival rate was significantly higher in the low CKS2 expression group (59.9%) than in the high CKS2 expression group (23.9%) (p<0.01). Univariate and multivariate analysis showed that CKS2 expression status was an independent prognostic factor (relative risk, 1.41; 95% confidence interval, 1.01-1.97; p<0.05). Moreover, the inhibition of cellular proliferation by CKS2-siRNA was observed in a gastric cancer cell line. CKS2 is one of the gastric cancerrelated genes that correlates with biological aggressiveness and poor prognosis of gastric cancer. Thus, CKS2 is a possible candidate gene for diagnosis, as well as targeted molecular diagnosis and therapy in gastric cancer.

PSMB8 and PBK as potential gastric cancer subtype-specific biomarkers associated with prognosis

“…Of the 116 genes highly expressed in the C2 subtype, 22 were associated with these GO terms and KEGG pathways, most of which are implicated in cancer: Ribosomal protein (RP)-encoding genes RPL6 , RPLP0 , RPL8 , RPS6P1 , PRS7 , and RPL29 [9], eukaryotic translation elongation factor EEF1B2 [10], eukaryotic translation initiation factor EIF5A [11], mRNA export factor THOC4 [12], heterogeneous nuclear ribonucleoprotein HNRNPA1 [13], mitotic arrest deficiency 2 MAD2 [14], proteasome subunits PSMA6 and PSMB8 [15], protein kinase regulatory subunit CKS2 [16], and PDZ-binding kinase PBK [17]. These results suggest that altered expression of these identified genes could reflect the specific molecular and biological features of gastric cancer cells.…”

Depletion of Cks1 and Cks2 expression compromises cell proliferation and enhance chemotherapy-induced apoptosis in HepG2 cells

“…The caspase family of proteins play a critical role in mediating cellular apoptosis. It has been reported that Cks2 downregulation reduces cell proliferation and increase caspase-3 activation and Bax expression in gastric cancer cells ( 6 ). Depleting Cks2 expression with siRNA in esophageal squamous cell carcinoma also results in reducing cell proliferation ( 13 ).…”

Mitochondrial Function of CKS2 Oncoprotein Links Oxidative Phosphorylation with Cell Division in Chemoradioresistant Cervical Cancer

“…CDK regulatory subunit 2 (CKS2) is overexpressed and associated with aggressiveness of many human malignancies, including cancer of the uterine cervix, prostate, gastrointestinal tract, bile duct, breast, and liver [1], [2], [3], [4], [5], [6], [7], [8], [9]. In cervical cancer, high CKS2 expression has been associated with presence of lymph node metastases at diagnosis and poor survival following chemoradiotherapy [2].…”

“…In cervical cancer, high CKS2 expression has been associated with presence of lymph node metastases at diagnosis and poor survival following chemoradiotherapy [2]. Overexpression of CKS2 in cell lines from a variety of cancer types has been shown to promote cell proliferation, whereas CKS2 knockdown induced cell cycle arrest and apoptosis and inhibited cell growth, migration, and tumorigenesis in mice [1], [3], [6], [9], [10]. CKS2 has therefore been suggested as a new candidate biomarker and therapeutic target; however, a better understanding of its role in cancer pathogenesis is required before the findings can be fully exploited in the clinic [11].…”