Downregulated CDKN1C/p57(kiP2) drives tumorigenesis and associates with poor overall survival in breast cancer

CDKN1C, also known as p57(kiP2), is considered to be a potential tumor suppressor implicated in several kinds of human cancers. However, the current knowledge of CDKNIC in breast cancer remains obscure. In the present study, we demonstrated that CDKNIC 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 CDKNIC was correlated with age and tumor size in the TCGA cohort containing 708 cases of breast cancer. Low expression of CDKNIC 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 mTORCI and PI3K/Akt/mTOR. In conclusion, our data suggested an essential role of CDKNIC in the tumorgenesis of breast cancer. Targeting CDKNIC may be a promising strategy for anticancer therapeutics. (C) 2018 Elsevier Inc. All rights reserved.