中文摘要：

葡萄糖6-磷酸脱氢酶（glucose 6-phosphate dehydrogenase,G6PD）为磷酸戊糖途径的调节酶。研究表明,G6PD与多种恶性肿瘤的发生密切相关。然而,G6PD在肾透明细胞癌（clear cell renal cell carcinoma,ccRCC）中的功能及其作用机制却鲜有报道。本研究通过TCGA数据分析发现,G6PD在肾透明细胞癌TNMⅢ/Ⅳ期mRNA表达水平显著升高,与患者的性别、原发肿瘤直径、淋巴结转移、远端转移、病灶一侧的偏重性、病理分级以及TNM临床分期密切相关。并且,G6PD异常激活有可能成为评价肾透明细胞癌患者不良预后的分子。细胞系检测结果提示,与对照293T细胞及恶性程度较低的786-O细胞相比,恶性程度较高的Caki-1细胞中的G6PD表达及活性明显增加。基因稳定转染结合CCK8分析结果显示,G6PD过表达或异常激活可显著提高293T及786-O细胞的增殖能力,并且促进786-O细胞中周期蛋白D1基因表达上调。综上,本研究通过TCGA数据库分析和稳定细胞系检测及CCK8分析,结果显示,G6PD在肾透明细胞癌中异常激活,并可上调细胞周期蛋白D1表达,进而促进肿瘤细胞增殖。该研究为进一步揭示肾透明细胞癌分子发病机制以及开发有效的靶向治疗方案提供了借鉴。

英文摘要：

Glucose 6-phosphate dehydrogenase（G6PD） is a critical enzyme of the pentose phosphate pathway（PPP）.It has been demonstrated that aberrant expression of G6PD is closely related to the pathogenesis and development of several malignant tumors.However,the role of G6PD in clear cell renal cell carcinoma（ccRCC） is still unclear.Based on the comprehensive analyses of TCGA database,we constructed stable cell lines and performed cell proliferation assays,aiming to study the expression profile of G6PD in ccRCC.We found that G6PD mRNA increased evidently in the Tumor Node Metastasis（TNM） III/IV stage of ccRCC via TCGA analysis.Up-regulated G6PD correlates with patients’ gender,the tumor（T） stage,the node（N） stage,the metastasis（M） stage,tumor laterality,pathological grade as well as clinical TNM stages.Moreover,G6PD overexpression is also associated with poorer overall survivals in ccRCC.Compared to 293 T and 786-O cells,which were considered as less malignant cells,the metastatic Caki-1 cell line had higher G6PD expression levels.Gene transfection and CCK8 assays showed that overexpression or activation of G6PD promoted 293T（control） and 786-O cell proliferation,and increased the expression of cyclin D1 in 786-O cells.Taken together,the results demonstrate that G6PD overexpression promotes cellular proliferation of ccRCC.This study may provide new reference for ccRCC pathogenesis investigation and improve current therapeutic approaches.