Expression and Clinical Significance of CIP2A in Bladder Urothelial Cell Carcinoma
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摘要: 目的 研究蛋白磷酸酶2A癌性抑制因子(cancerous inhibitor of protein phosphatase 2A,CIP2A)在膀胱尿路上皮癌组织中的表达及其与临床病理特征的关系，探讨其成为膀胱尿路上皮癌预后指标的可行性。方法 应用RT-PCR和Western blot检测CIP2A mRNA和蛋白在25例膀胱尿路上皮癌和对应癌旁组织中的表达情况；应用组织芯片技术和免疫组织化学方法，检测CIP2A在117例膀胱尿路上皮癌和30例癌旁组织中的表达情况，分析CIP2A与膀胱尿路上皮癌患者临床病理特征及预后之间的关系。结果 CIP2A mRNA和蛋白在25例配对膀胱尿路上皮癌组织中的表达水平明显高于癌旁组织。免疫组织化学检测发现，膀胱尿路上皮癌组织中CIP2A蛋白的阳性表达率为76.9% (90/117)，明显高于癌旁组织的6.7% (2/30)，差异有统计学意义(P＜0.001)。CIP2A表达与肿瘤病理分级(P＜0.001)、临床分期(P＜0.001)、肿瘤大小(P=0.002)和淋巴结转移(P=0.046)有关，但与年龄、性别及肿瘤数目无关(P＞0.05)。Kaplan-Meier单因素分析显示，CIP2A蛋白高表达是总体生存率和无复发生存率的影响因素(P＜0.001)。Cox多因素风险比例模型显示，与总生存率相关的独立预后因素为临床分期、肿瘤病理分级和CIP2A表达，与无复发生存率相关的独立预后因素亦为临床分期、肿瘤病理分级和CIP2A表达。结论 CIP2A 蛋白在膀胱尿路上皮癌组织中高表达，可能与膀胱尿路上皮癌的进展有关，其表达状态是膀胱尿路上皮癌患者独立预后因素。Abstract: Objective To investigate the expression of cancerous inhibitor of protein phosphatase 2A (CIP2A) in bladder urothelial carcinoma tissues and its relationship with clinical pathologic characteristics，and to discuss the feasibility of CIP2A as prognostic markers. Methods RT-PCR and Western blot were used to evaluate the mRNA and protein expression of CIP2A in cancer tissues and corresponding paracancerous tissues from 25 bladder urothelial carcinoma patients.A tissue microarray (TMA) containing specimens from 117 bladder urothelial cell carcinoma tissues and 30 paracancerous tissues was constructed and then immunohistochemistry was used to examine the protein expression of CIP2A.The correlations between CIP2A and clinicopathological characteristics and prognosis were also analyzed. Results CIP2A mRNA and protein were undetectable or very low in paracancerous tissues,but were dramatically elevated in cancer samples in 25 patients.The positive expression rate of CIP2A protein in bladder urothelial cell carcinoma tissues [76.9% (90/117)] was significantly higher than that in paracancerous tissues [6.7% (2/30)].Such difference had statistic significance(P＜0.001).CIP2A expression correlated with histological grade (P＜0.001),tumor stage (P＜0.001),tumor diameter (P=0.002) and lymph nodes metastasis (P=0.046)；while it was not related with age,gender,tumor number and tumor recurrence (P＞0.05).Kaplan-Meier univariate analysis showed that the overall and recurrence-free survival rates were significantly higher in the group with low expression of CIP2A than in the group with high expression of CIP2A (P＜0.001).Cox proportional hazards model revealed that tumor stage，histological grade,and CIP2A expression were independent predictors of an unfavorable prognosis for overall survival rate (P＜0.001,P=0.001 and P=0.035,respectively ) and recurrence-free survival rates (P＜0.001,P＜0.001 and P=0.003,respectively ). Conclusion The expression of CIP2A protein is significantly increased in bladder urothelial cell carcinoma tissues,which may be involved in the progress of bladder urothelial cell carcinoma.CIP2A may be a valuable biomarker for assessing the prognosis of bladder urothelial cell carcinoma.
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Key words:
- Bladder urothelial cell carcinoma /
- Immunohistochemistry /
- Gene expression /
- Progno-sis /
- CIP2A
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[1] [1]Junttila MR,Puustinen P,Niemel M,et al.CIP2A Inhibits PP2A in Human Malignancies[J].Cell,2007,130(1):51-62. [2] Khanna A,Bckelman C,Hemmes A,et al.MYC-dependent regulation and prognostic role of CIP2A in gastric cancer[J].J Natl Cancer Inst,2009,101(11):793-805. [3] Bockelman C,Hagstrm J,Mkinen LK,et al.High CIP2A immunoreactivity is an independent prognostic indicator in early-stage tongue cancer[J].Br J Cancer,2011,104(12):1890-5. [4] Ma L,Wen ZS,Liu Z,et al.Overexpression and small molecule-triggered downregulation of CIP2A in lung cancer[J].PLoS One,2011,6(5):e20159. [5] Dong QZ,Wang Y,Dong XJ,et al.CIP2A is overexpressed in non-small cell lung cancer and correlates with poor prognosis[J].Ann Surg Oncol,2011,18(3):857-65. [6] Basile JR,Czerninski R.The role of CIP2A in oral squamous cell carcinoma[J].Cancer Biol Ther,2010,10(7):700-2. [7] Chen KF,Liu CY,Lin YC,et al.CIP2A mediates effects of bortezomib on phospho-Akt and apoptosis in hepatocellular carcinoma cells[J].Oncogene,2010,29(47):6257-66. [8] Cme C,Laine A,Chanrion M,et al.CIP2A is associated with human breast cancer aggressivity[J].Clin Cancer Res,2009,15(16):5092-100. [9] Bckelman C,Koskensalo S,Hagstrm J,et al.CIP2A overexpression is associated with c-Myc expression in colorectal cancer[J].Cancer Biol Ther,2012,13(5):289-95. [10] Ren J,Li W,Yan L,et al.Expression of CIP2A in renal cell carcinomas correlates with tumour invasion,metastasis and patients' survival[J].Br J Cancer,2011,105(12):1905-11. [11] Bckelman C,Lassus H,Hemmes A,et al.Prognostic role of CIP2A expression in serous ovarian cancer[J].Br J Cancer,2011,105(7):989-95. [12] Teng HW,Yang SH,Lin JK,et al.CIP2A is a predictor of poor prognosis in colon cancer[J].J Gastrointest Surg,2012,16(5):1037-47. [13] Xue YJ,Lu Q,Sun ZX.CD147 overexpression is a prognostic factor and a potential therapeutic target in bladder cancer[J].Med Oncol,2011,28 (4):1363-72.
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