Downregulation of FBP1 Promotes Tumor Metastasis and Indicates Poor Prognosis in Gastric Cancer via Regulating Epithelial-Mesenchymal Transition.
Downregulation of FBP1 Promotes Tumor Metastasis and Indicates Poor Prognosis in Gastric Cancer via Regulating Epithelial-Mesenchymal Transition.
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DOI：
10.1371/journal.pone.0167857
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Xu LC
中科院分区：
文献类型：
--
作者：
Li J;Wang Y;Li QG;Xue JJ;Wang Z;Yuan X;Tong JD;Xu LC
最近的研究表明，一些糖酵解酶是复杂的，多方面的蛋白质，而不是简单的糖酵解途径的组成部分。FBP 1在葡萄糖代谢中起重要作用，但其在胃癌发生和转移中的作用尚未完全了解。FBP 1的预后价值首先在癌症基因组图谱（TCGA）数据库中研究，并在内部数据库中验证。在体外检测FBP 1对细胞增殖和转移的影响。采用非参数检验和Log-rank检验评价FBP 1表达的临床意义。在TCGA队列中，FBP 1 mRNA水平被证明是胃癌总生存率的预测因子（P = 0.029）。在验证队列中，FBP 1表达与晚期N分期（P = 0.021）和淋巴管浸润（P = 0.011）呈负相关。多因素考克斯回归分析显示，FBP 1是总生存期（P = 0.004）和无病生存期（P<0.001）的独立预测因子。功能研究表明，异位表达FBP 1抑制胃癌细胞的增殖和侵袭，而沉默FBP 1表达则相反（P<0.05）。在机械上，FBP 1通过抑制上皮-间充质转化（EMT）而充当肿瘤抑制因子。FBP 1的下调通过促进EMT促进胃癌转移，是胃癌潜在的预后因子和治疗靶点。
Recent studies indicated that some glycolytic enzymes are complicated, multifaceted proteins rather than simple components of the glycolytic pathway. FBP1 plays a vital role in glucose metabolism, but its role in gastric cancer tumorigenesis and metastasis has not been fully understood. The prognostic value of FBP1 was first studied in The Cancer Genome Atlas (TCGA) database and validated in in-house database. The effect of FBP1 on cell proliferation and metastasis was examined in vitro. Nonparametric test and Log-rank test were used to evaluate the clinical significance of FBP1 expression. In the TCGA cohort, FBP1 mRNA level were shown to be predictive of overall survival in gastric cancer (P = 0.029). In the validation cohort, FBP1 expression were inversely correlated with advanced N stage (P = 0.021) and lymphovascular invasion (P = 0.011). Multivariate Cox regression analysis demonstrated that FBP1 was an independent predictor for both overall survival (P = 0.004) and disease free survival (P<0.001). Functional studies demonstrated that ectopic FBP1 expression inhibited proliferation and invasion in gastric cancer cells, while silencing FBP1 expression had opposite effects (P<0.05). Mechanically, FBP1 serves as a tumor suppressor by inhibiting epithelial-mesenchymal transition (EMT). Downregulation of FBP1 promotes gastric cancer metastasis by facilitating EMT and acts as a potential prognostic factor and therapeutic target in gastric cancer.
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