Phosphoglycerate dehydrogenase is a novel predictor for poor prognosis in gastric cancer.
Phosphoglycerate dehydrogenase is a novel predictor for poor prognosis in gastric cancer.
复制标题
磷酸甘油酸脱氢酶是胃癌不良预后的新预测因子
DOI：
10.2147/ott.s105787
复制
发表时间：
2016
影响因子：
4
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Xian Y;Zhang S;Wang X;Qin J;Wang W;Wu H
目的磷酸甘油酸脱氢酶（PHGDH）是丝氨酸生物合成限速步骤中的关键代谢酶，在多种肿瘤的转移中起重要作用。本研究旨在探讨PHGDH在胃癌中的预后价值。方法采用实时荧光定量聚合酶链反应（real-time polymerase chain reaction，RT-PCR）技术检测20例胃癌组织及癌旁组织中PHGDH mRNA的表达。PHGDH的免疫组化进行组织芯片，包括482 GC和64匹配的相邻的非肿瘤组织从手术中获得，20慢性胃炎，18肠上皮化生，和31低级别和66高级别上皮内瘤变通过胃镜活检获得。使用单变量和多变量考克斯比例风险模型进行生存分析。结果PHGDH mRNA及其蛋白产物在胃癌组织中的表达均呈GC组织偏好性。PHGDH的高表达与组织学类型（P=0.011）、肿瘤分期（P=0.014）和术前癌胚抗原（P<0.001）有关。PHGDH表达与胃癌患者5年生存率呈负相关。此外，多因素分析表明PHGDH是胃癌预后的独立预后因素。结论PHGDH对于预测患者结局非常重要，并且是开发GC治疗方法的潜在目标。
Purpose Phosphoglycerate dehydrogenase (PHGDH) acts as a key metabolic enzyme in the rate-limiting step in serine biosynthesis and plays an important role in metastasis of several cancers. The aim of this study was to investigate the prognostic value of PHGDH in gastric cancer (GC). Methods The messenger RNA expression of PHGDH was determined in 20 pairs of cancerous and adjacent nontumor tissues by real-time polymerase chain reaction. Immunohistochemistry of PHGDH was performed on tissue microarray, composed of 482 GC and 64 matched adjacent nontumor tissues acquired from surgery, 20 chronic gastritis, 18 intestinal metaplasia, and 31 low-grade and 66 high-grade intraepithelial neoplasias acquired through gastric endoscopic biopsy. Univariate and multivariate Cox proportional hazard models were used to perform survival analyses. Results Both PHGDH messenger RNA and protein product exhibited GC tissue-preferred expression, when compared with benign tissues. The high PHGDH expression was significantly correlated with histological type (P=0.011), tumor stage (P=0.014), and preoperative carcinoembryonic antigen (P<0.001). A negative correlation was found between PHGDH expression and the 5-year survival rate of patients with GC. Furthermore, multivariate analysis indicated that PHGDH was an independent prognostic factor for outcome in GC. Conclusion PHGDH is important in predicting patient outcomes and is a potential target for the development of therapeutic approaches to GC.