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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 the expression of glucose-6-phosphatase catalytic subunit (G6PC) and disease prognosis in high-grade serous ovarian cancer (HGS-OvCa) and the related protein expression changes. Methods One hundred and eighty-eight cases of RNA-seq sequencing were selected from the HGS-OvCa Provisional database. The genes related to glucose metabolism regulation were obtained by MSig DB. The expression of these genes in ovarian cancer tissues and Adjacent normal ovarian tissue is there any difference. Then combined with the clinical data of patients with ovarian cancer G6PC expression were significantly different cases of survival analysis, evaluate the relationship with the prognosis of the disease. At the same time, the level of protein expression in G6PC differentially expressed cases was compared by analyzing protein level data detected by reverse phase matrix array (RPPA) in cancer genome map (TCGA). RESULTS: G6PC was highly expressed in 17.09% of HGS-OvCa tissues, of which G6PC gene fragments were amplified in 2 of the tissues. In the analysis of clinicopathological parameters, the expression of G6PC had no significant correlation with them. However, in terms of tumor recurrence and prognosis, the high expression of G6PC was negatively correlated with the progression-free survival and overall survival of patients. Reverse phase protein array RPPA method analysis of G6PC overexpression in ovarian cancer patients with protein expression changes, including CDKN1B encoding protein p27 and phosphorylation levels were significantly reduced. Conclusion The high expression of G6PC has a significant correlation with short-term tumor recurrence and poor prognosis. G6PC is expected to be one of the predictors of prognosis and recurrence of ovarian cancer. In ovarian cancer tissues upregulated at G6PC level, the expression of CDKN1B protein and phosphorylated protein decreased most significantly. G6PC may be a new target for the treatment of ovarian cancer.