癌蛋白CIP2A与多发性骨髓瘤患者预后不良相关性研究

Overexpression of CIP2A Oncoprotein Is Associated with Poor Prognosis in Human Multiple Myeloma

目的:探讨蛋白磷酸酶2A(protein phosphatase 2A,PP2A)的内源性癌性抑制因子(cancerous inhibitor of protein phosphatase 2A,CIP2A)在多发性骨髓瘤(multiple myeloma,MM)患者组织及细胞系中的表达情况及其对MM预后的影响。方法:使用Western blot、实时定量PCR(QPCR)检测CIP2A在不同MM细胞系的表达情况;采用QPCR检测11例患者肿瘤组织及4例正常组织中CIP2A的表达;通过免疫组化方法检测CIP2A在41例MM患者组织和22例对应正常BM组织中的表达;统计分析CIP2A表达水平与临床病理及预后的相关性。结果:CIP2A在MM细胞系中mRNA和蛋白质水平上均存在过表达。CIP2A在患者骨髓瘤细胞中的表达量显著高于健康志愿者正常外周血单核细胞。与癌旁组织相比,CIP2A表达量在MM患者组织中显著上调。CIP2A高表达的MM患者总体生存率显著低于CIP2A低表达患者。结论:CIP2A在MM患者中存在过表达,且与患者预后不良显著相关。CIP2A可能作为MM的诊断标志物及潜在药物治疗靶点。

Objective Cancerous inhibitor of protein phosphatase 2 A（ CIP2A） oncoprotein,an inhibitor of protein phosphatase 2 A（ PP2A）,is abnormally expressed in many cancers. In this study,we investigated the expression of CIP2A in multiple myeloma（ MM） and its effect on MM prognosis. Methods Western blot and qPCR were used to detect the expression of CIP2A in different MM cell lines. The expression of CIP2A was also studied by qPCR in 11 cases of tumor tissues and 4 normal tissues; the expression of CIP2A in 41 MM samples and 22 normal BM tissues was detected by immunohistochemistry; Statistical analysis was used to detect the correlation between CIP2A expression and clinicopathological features. Results CIP2A was overexpressed in MM cell line at the mRNA and protein levels. The expression of CIP2A in MM patients＇ samples was significantly higher than that in normal cells. The overall survival rate of MM patients with high expression of CIP2A was significantly lower than that of patients with low expression of CIP2A. Conclusion CIP2A is overexpressed in patients with MM and is significantly associated with poor prognosis. CIP2A may be a diagnostic marker of MM and potential target for drug treatment.