Glutamate dehydrogenase is a novel prognostic marker and predicts metastases in colorectal cancer patients.
Glutamate dehydrogenase is a novel prognostic marker and predicts metastases in colorectal cancer patients.
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谷氨酸脱氢酶是一种新型预后标志物，可预测结直肠癌患者的转移
DOI：
10.1186/s12967-015-0500-6
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发表时间：
2015-05-07
影响因子：
7.4
通讯作者：
Zeng B
中科院分区：
文献类型：
--
作者：
Liu G;Zhu J;Yu M;Cai C;Zhou Y;Yu M;Fu Z;Gong Y;Yang B;Li Y;Zhou Q;Lin Q;Ye H;Ye L;Zhao X;Li Z;Chen R;Han F;Tang C;Zeng B
谷氨酸脱氢酶（GDH）是催化谷氨酰胺代谢途径最终反应的关键酶，已报道与肿瘤生长和转移有关。然而，其临床意义及其在结直肠癌发病中的作用在很大程度上是未知的。采用qPCR、western blot和免疫组化检测结直肠癌细胞和标本中GDH的表达。分析GDH表达与临床病理特征及预后的相关性。评价GDH在结直肠癌细胞增殖、运动和转移中的功能作用。我们发现GDH在结直肠癌和转移性病变中均上调（n = 104）。GDH高表达患者的总生存率（HR 2.32; 95% CI 1.26-4.26; P = 0.007）和无病生存率（HR 2.48; 95% CI 1.25-4.92; P = 0.009）均低于GDH低表达患者。此外，我们发现GDH表达是结直肠癌的一个独立预后因素。此外，GDH的过表达促进了体外细胞的增殖、迁移和侵袭，而GDH的功能缺失则相反。最后，我们证明GDH对CRC进展的促进与STAT3介导的上皮-间质转化（EMT）诱导的激活相关。这些结果表明，GDH在结直肠癌的进展中起着关键作用，可能为结直肠癌的治疗提供新的代谢治疗靶点。本文的在线版本（doi:10.1186/s12967-015-0500-6）包含补充材料，可供授权用户使用。
Glutamate dehydrogenase (GDH) is a key enzyme that catalyzes the final reaction of the glutamine metabolic pathway, and has been reported implicated in tumor growth and metastasis. However, it’s clinical significance and role in colorectal cancer (CRC) pathogenesis is largely unknown. The expression of GDH was determined by qPCR, western blot and immunohistochemistry in CRC cells and samples. The correlation of GDH expression with clinicopathologic features and prognosis was analyzed. The functional role of GDH in CRC cell proliferation, motility and metastasis was evaluated. We found that GDH was up-regulated both in colorectal cancer and metastatic lesions (n = 104). Patients with high GDH expression had poorer overall survival (HR 2.32; 95% CI 1.26-4.26; P = 0.007) and poorer disease-free survival rates (HR 2.48; 95% CI 1.25-4.92; P = 0.009) than those with low GDH expression. Furthermore, we showed that GDH expression was an independent prognostic factor for CRC. In addition, over-expression of GDH promoted cell proliferation, migration and invasion in vitro, whereas loss function of GDH did the opposite. Finally, we demonstrated that the promotion of CRC progression by GDH correlated with activation of STAT3 mediated epithelial-mesenchymal transition (EMT) induction. These results indicate that GDH plays a critical role in CRC progression, and may provide a novel metabolism therapeutic target for CRC treatment. The online version of this article (doi:10.1186/s12967-015-0500-6) contains supplementary material, which is available to authorized users.
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影响因子：
4.7
作者：
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通讯作者：
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影响因子：
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作者：
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