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Cyclin-dependent kinase subunit 2 overexpression promotes tumor progression and predicts poor prognosis in uterine leiomyosarcoma.

ABSTRACT: Cyclin-dependent kinase subunit (CKS) 2 is a member of the CKS family, which plays an important role in the regulation of meiosis and mitosis. Overexpression of CKS2 has been reported in several types of tumors. However, few studies have investigated its role in uterine leiomyosarcoma (ULMS). In the present study, the expression of CKS2 in 38 cases of ULMS and 38 cases of uterine leiomyoma (ULM) was analyzed by immunohistochemistry. Moreover, the functional analysis of CKS2 was performed in ULMS cell lines. A significantly higher expression of CKS2 was found in ULMS tissues than in ULM tissues (P<0.01) and high CKS2 expression was associated with increased tumor size, low progesterone receptor expression and poor prognosis in patients with ULMS. Multivariate Cox regression analysis revealed that CKS2 expression status was an independent predictor of overall survival for ULMS. Furthermore, silencing of CKS2 in ULMS cells inhibited cell proliferation, colony formation, migration and invasion, and resulted in cell cycle arrest. In conclusion, the present study demonstrated that CKS2 may serve as a marker for the differential diagnosis of ULMS and ULM. In addition, it may act as an independent prognostic factor in patients with ULMS, and serve as a novel target for ULMS therapy.

SUBMITTER: Deng Y

PROVIDER: S-EPMC6704316 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Cyclin-dependent kinase subunit 2 overexpression promotes tumor progression and predicts poor prognosis in uterine leiomyosarcoma.

Deng Yupeng Y Han Qun Q Mei Shuyu S Li Hailing H Yang Fan F Wang Jun J Ge Shuang S Jing Xiaotong X Xu Hui H Zhang Tingguo T

Oncology letters 20190725 3

Cyclin-dependent kinase subunit (CKS) 2 is a member of the CKS family, which plays an important role in the regulation of meiosis and mitosis. Overexpression of CKS2 has been reported in several types of tumors. However, few studies have investigated its role in uterine leiomyosarcoma (ULMS). In the present study, the expression of CKS2 in 38 cases of ULMS and 38 cases of uterine leiomyoma (ULM) was analyzed by immunohistochemistry. Moreover, the functional analysis of CKS2 was performed in ULMS ...[more]

PMID: 31452763

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Project description:BackgroundThe mitochondrial pyruvate dehydrogenase complex (PDC) link glycolysis to the tricarboxylic acid cycle by decarboxylating pyruvate to acetyl coenzyme A irreversibly. Cancer cells are characterized by a shift in cellular metabolism from mitochondrial respiration to glycolysis. PDC activity inhibition mediated by phosphorylation via pyruvate dehydrogenase kinase (PDK) has been linked to cancer. However, the clinical significance of PDKs in urothelial cancer prognosis is not clear. We investigated the role and prognostic value of PDK3 expression in patients with upper urinary tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC).Patients and methodsWe retrospectively analyzed clinical data and pathological features. Formalin-fixed urothelial carcinoma (UC) tissues were collected and embedded in paraffin. The correlation of PDK3 expression with clinical characteristics, pathological findings and patient outcomes, including metastasis-free survival (MFS) and disease-specific survival (DSS) were analyzed by Pearson's chi-square test, Kaplan-Meier analysis, and the multivariate Cox proportional hazards model.ResultsData from 295 patients with UBUC and 340 patients with UTUC were evaluated. High PDK3 expression significantly correlated with several pathologic variables such as high T stage, lymph node metastases, high tumor grade, vascular invasion, and high mitotic rate (all P < 0.001). High PDK3 expression was associated with poor disease-specific survival (DSS) (P < 0.0001) and metastatic free survival (MFS) (P < 0.0001) in a Kaplan-Meier analysis. Additionally, multivariate analysis demonstrated increased PDK3 expression is a significant predictive risk factor for DSS [hazard ratio (HR) in UBUC, 2.79, P = 0.009; in UTUC, 2.561, P = 0.03] and MFS (HR in UBUC, 1.907, P = 0.024; in UTUC, 1.793, P = 0.044). The gene co-expression analysis showed abundant PDK3 co-upregulated genes were involved in the processes of DNA replication and repair through the Gene Ontology classification system.ConclusionHigh PDK3 expression has been linked to negative pathologic characteristics and poor oncological outcomes, suggesting that it could be used as a predictive biomarker for UC. PDK3 mRNA levels and its co-upregulated genes were strongly associated with DNA replication and repair. These results suggest that PDK3 may play a key role in tumor proliferation and development.

Dataset Information

Cyclin-dependent kinase subunit 2 overexpression promotes tumor progression and predicts poor prognosis in uterine leiomyosarcoma.

Publications

Cyclin-dependent kinase subunit 2 overexpression promotes tumor progression and predicts poor prognosis in uterine leiomyosarcoma.

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