Overexpression of G6PD Represents a Potential Prognostic Factor in Clear Cell Renal Cell Carcinoma.
Overexpression of G6PD Represents a Potential Prognostic Factor in Clear Cell Renal Cell Carcinoma.
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G6PD 过度表达是透明细胞肾细胞癌的潜在预后因素
DOI：
10.7150/jca.16858
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发表时间：
2017
影响因子：
3.9
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
Zhang Q;Yi X;Yang Z;Han Q;Di X;Chen F;Wang Y;Yi Z;Kuang Y;Zhu Y
葡萄糖-6-磷酸脱氢酶（G6 PD）参与葡萄糖代谢，是戊糖磷酸途径（PPP）的限速酶。最近，G6 PD失调已在多种人类癌症中被发现。通过分析癌症基因组图谱（TCGA）中发表的数据，我们的初步研究表明，G6 PD mRNA表达在晚期Fuhrman分级的肾透明细胞癌（ccRCC）中显著较高。这些线索促使我们进一步评估G6 PD的表达谱及其对ccRCC患者预后的影响。在这项研究中，使用免疫组织化学分析了149例人ccRCC和正常组织中的G6 PD表达水平。结果显示，与正常肾组织相比，51.0%的ccRCC组织中G6 PD呈高表达（p<0.05）。G6 PD的高表达与肿瘤范围、淋巴结转移、Fuhrman分级和TNM分期显著相关（均p<0.05）。此外，在ccRCC中，阳性G6 PD表达与较差的总体存活相关（p<0.001）。在考克斯回归分析中，G6 PD的高表达也可能是ccRCC总生存期的独立预后因素（p=0.007）。这项研究表明，G6 PD的过表达与晚期疾病状态相关，因此可能成为ccRCC预后不良的重要指标，以及开发有效治疗方式的潜在治疗靶点。
Glucose-6-phosphate dehydrogenase (G6PD) participates in glucose metabolism and it acts as the rate-limiting enzyme of the pentose phosphate pathway (PPP). Recently, G6PD dysregulation has been found in a variety of human cancers. Through analyzing published data in The Cancer Genome Atlas (TCGA), our pilot study indicated that G6PD mRNA expression was significantly higher in advanced Fuhrman grade in clear cell renal cell carcinoma (ccRCC). These clues promoted us to further evaluate the expression profile of G6PD and its prognostic impact in patients with ccRCC. In this study, G6PD expression levels were analyzed in 149 human ccRCC and normal tissues using immunohistochemistry. The results showed that compared with that in the normal renal samples, G6PD was found highly expressed in 51.0% of ccRCC (p<0.05). High expression of G6PD was significantly correlated to tumor extent, lymph node metastasis, Fuhrman grade, and TNM stage of ccRCC (all p<0.05). Moreover, positive G6PD expression was associated with poorer overall survival in ccRCC (p<0.001). In Cox regression analyses, high expression of G6PD also could be an independent prognostic factor for overall survival in ccRCC (p=0.007). This study suggests that overexpression of G6PD is associated with advanced disease status and therefore may become an important prognosticator for poor outcomes in ccRCC, as well as a potential therapeutic target for developing effective treatment modalities.