Downregulated CDKN1C/p57kip2 drives tumorigenesis and associates with poor overall survival in breast cancer

CDKN1C, also known as p57kip2, is considered to be a potential tumor suppressor implicated in several kinds of human cancers. However, the current knowledge of CDKN1C in breast cancer remains obscure. In the present study, we demonstrated that CDKN1C was dramatically downregulated in breast cancer c...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2018-02, Vol.497 (1), p.187-193
Main Authors: Qiu, Zhu, Li, Yunhai, Zeng, Beilei, Guan, Xiaoqin, Li, Hongzhong
Format: Article
Language:English
Subjects:
Breast cancer
CDKN1C
GSEA
p57
Prognosis
TCGA
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Summary:CDKN1C, also known as p57kip2, is considered to be a potential tumor suppressor implicated in several kinds of human cancers. However, the current knowledge of CDKN1C in breast cancer remains obscure. In the present study, we demonstrated that CDKN1C was dramatically downregulated in breast cancer compared with normal tissues by using real-time quantitative polymerase chain reaction, western blot and two public data portals: The Cancer Genome Atlas (TCGA) and Oncomine datasets. Moreover, the expression of CDKN1C was correlated with age and tumor size in the TCGA cohort containing 708 cases of breast cancer. Low expression of CDKN1C was significantly associated with poor overall survival (OS) in the TCGA cohort and validated cohort composed of 1402 patients. Multivariate Cox regression analysis indicated that CDKN1C was an independent prognostic factor for worse OS (HR = 1.78, 95% CI: 1.09–2.89, p = 0.020). Furthermore, gene set enrichment analysis (GSEA) revealed that CDKN1C was significantly correlated with gene signatures involving DNA repair, cell cycle, glycolysis, adipogenesis, and two critical signaling pathways mTORC1 and PI3K/Akt/mTOR. In conclusion, our data suggested an essential role of CDKN1C in the tumorgenesis of breast cancer. Targeting CDKN1C may be a promising strategy for anticancer therapeutics. •CDKN1C is downregulated in breast cancer.•Low expression of CDKN1C is significantly associated with poor overall survival.•CDKN1C is an independent prognostic factor for breast cancer patients.•CDKN1C is implicated in critical biological processes and signaling pathways in breast cancer progression.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2018.02.052