title: CIP2A is a predictor of survival and a novel therapeutic target in bladder urothelial cell carcinoma.
abstract: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified human oncoprotein that stabilizes the c-MYC protein. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in urothelial cell carcinoma (UCC) of the bladder. CIP2A expression was examined in 20 fresh bladder UCC tissues and paired adjacent normal bladder tissues by RT-PCR and Western blot. Immunohistochemistry for CIP2A was performed on additional 117 bladder UCC tissues. The clinical significance of CIP2A expression was analyzed. CIP2A downregulation was performed in bladder UCC cell line T24 with high abundance of CIP2A, and the effects of CIP2A silencing on cell proliferation, migration, invasion in vitro, and tumor growth in vivo were evaluated. We found that CIP2A expression was upregulated in bladder UCC tissues relative to adjacent normal bladder tissues. Clinicopathological analysis showed that CIP2A expression was significantly associated with tumor stage (P = 0.004), histological grade (P = 0.007), and lymph node status (P = 0.001). The Kaplan-Meier survival curves revealed that CIP2A expression was associated with poor prognosis in bladder UCC patients (log-rank value = 14.704, P < 0.001). CIP2A expression was an independent prognostic marker of overall patient survival in a multivariate analysis (P = 0.015). Knockdown of the CIP2A expression reduced cell proliferation, anchorage-independent growth, migration, invasion, and tumor growth in xenograft model mice. Our findings suggest that CIP2A is an independent predictor of poor prognosis of bladder UCC patients, and inhibition of its expression might be of therapeutic significance.
authors.affiliation: Department of Urology, First Affiliated Hospital of Gannan Medical University, No. 23, Qing Nian Road, Ganzhou 341000, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Xue
authors.forename: Gengqing
authors.initials: G
authors.lastname: Wu
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zou
authors.forename: Guoxi
authors.initials: G
authors.lastname: Zhang
authors.forename: Rihai
authors.initials: R
authors.lastname: Xiao
authors.forename: Yuanhu
authors.initials: Y
authors.lastname: Yuan
authors.forename: Dazhi
authors.initials: D
authors.lastname: Long
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Yuting
authors.initials: Y
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Folin
authors.initials: F
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001324:Autoantigens / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D001324:Autoantigens; D014408:Biomarkers, Tumor; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins