出 处:《中国妇幼保健》2017年第16期3928-3931,共4页Maternal and Child Health Care of China
摘 要:目的探索高级别浆液性卵巢癌(HGS-OvCa)中葡萄糖-6-磷酸酶催化亚基(G6PC)的表达与疾病预后的关系及相关蛋白表达水平的改变。方法选择HGS-OvCa Provisional数据库中完成RNA-seq深度测序的病例158例,通过分子特征数据库(MSig DB)获得葡萄糖代谢调节的相关基因,使用c Bio Portal软件分析这些基因的表达在卵巢癌组织和癌旁正常卵巢组织中是否存在差异。随后结合卵巢癌患者临床资料对G6PC表达存在显著差异的病例进行生存分析,评价其与疾病预后的关系。同时通过分析癌症基因组图谱(TCGA)中反相蛋白质阵列基因芯片(RPPA)检测的蛋白水平数据,比较G6PC差异表达的病例中蛋白表达水平的改变。结果 17.09%的HGS-OvCa组织中G6PC高表达,其中2例组织存在G6PC基因片段扩增。在临床病理指标分析中,G6PC的表达与其均无显著相关性。但是在肿瘤复发以及预后的指标方面,G6PC的高表达与患者的无进展生存期及总生存期呈显著负相关。反相蛋白阵列RPPA方法分析G6PC高表达卵巢癌患者中蛋白水平表达的改变,其中CDKN1B编码蛋白p27及其磷酸化水平均发生了显著下调。结论 G6PC的高表达与肿瘤短期复发及预后不良有显著的相关性,G6PC有望作为卵巢癌预后及复发的预测指标之一。在G6PC水平上调的卵巢癌组织中,CDKN1B编码蛋白及其磷酸化蛋白表达下降最为显著。G6PC可能是个体化卵巢癌治疗的新靶点。Objective To explore the relationship between expression of glucose-6-phosphatase,catalytic subunit( G6PC) in high-grade serous ovarian cancer( HGS-OvCa) and prognosis of the disease,and the change of relevant protein expression level.Methods A total of 158 cases with complete RNA-seq deep sequence in HGS-OvCa Provisional database were selected to obtain the genes involved in regulation of glucose metabolism by analyzing MSig DB,c Bio Portal software was used to analyze the difference of relevant gene expressions between ovarian carcinoma tissues and normal ovarian tissues adjacent to the cancer. Then survival analysis was used to evaluate the relationship between the cases with significant differences on G6 PC expression and prognosis of the disease in combination with clinical data of ovarian cancer patients. At the same time,the changes of protein expression level of cases with differential expression in G6 PC were compared through analyzing protein level data in TCGA with anti-phase protein array gene chip( RPPA) test. Results Among the158 HSG-OvCa patients,27 patients( 17. 09%) exhibited upregulated G6 PC gene expression,of which 2 patients were found with G6 PC gene fragments amplification. There was no significant correlation between G6 PC expression and clinical parameters. In the aspects of tumor recurrence and prognosis,G6 PC high expression was significantly negatively correlated with progression free survival and overall survival.RPPA method analyzed the changes of protein expression level of ovarian cancer patiens with upregulated G6 PC expression,protein and phosphorylation levels of p27 encoded by CDKN1 B were down-regulated significantly. Conclusion There is significiant correlation between upregulated G6 PC expression and short-term tumor recurrence and poor prognosis,G6 PC is expected to be one of the predictive indicators of prognosis and relapse of ovarian cancer. Among ovarian cancer tissues with upregulated G6 PC expression,the reduction of CDKN1 B coding protein and phosphor
关 键 词:高级别浆液性卵巢癌 葡萄糖-6-磷酸酶催化亚基 疾病预后
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