The correlation between NEDD4L and HIF-1α levels as a gastric cancer prognostic marker
The correlation between NEDD4L and HIF-1α levels as a gastric cancer prognostic marker
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DOI：
10.7150/ijms.34646
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发表时间：
2019-01-01
影响因子：
3.6
通讯作者：
Li, Yongxiang
中科院分区：
文献类型：
--
作者：
Jiang, Xingwang;Zhang, Shangxin;Li, Yongxiang
NEDD4L（神经前体细胞表达发育下调 4 样）蛋白是泛素连接酶 Nedd4 家族的成员。尽管研究表明 Nedd4L 可能在包括胃癌 (GC) 在内的多种癌症中充当肿瘤抑制因子，但其临床意义和在 GC 中的诊断价值尚不明确。 HIF-1α（转录因子的缺氧诱导因子家族）积极参与许多肿瘤的代谢，尽管其表达水平与GC中的临床意义之间的关系仍需确定。在本研究中，通过蛋白质印迹和定量 PCR (qPCR) 测定了 25 个新鲜冷冻的 GC 和匹配的正常组织中 HIF-1 α 和 NEDD4L mRNA 和蛋白的水平。此外，还进行了免疫组织化学测定，以测量 124 例 GC 和 25 例正常对照组织中 NEDD4L 和 HIF-1 α 的蛋白水平。我们观察到GC组织中NEDD4L mRNA和蛋白水平显着降低（P < 0.001），而HIF-1 α的水平升高（P < 0.001），两者均与不良预后相关，NEDD4L较低和HIF-1 α表达较高的患者也是如此（P < 0.001）。相关分析显示，NEDD4L 和 HIF-1 α 表达之间存在显着负相关（r = 0.288，P < 0.01）。多变量分析显示，NEDD4L（P < 0.05）和HIF-1 α（P < 0.001）的共表达是GC预后的独立预测因子。因此，NEDD4L 和 HIF-1 α 水平的相关性可以作为 GC 的预后标志物。
NEDD4L (neural precursor cell expressed developmentally down-regulated 4-like) protein is a member of ubiquitin ligases Nedd4 family. Although studies have shown that Nedd4L may act as a tumor suppressor in various cancers, including gastric cancer (GC), its clinical significance and the diagnostic value in GC is not well defined. HIF-1 alpha (hypoxia inducible factor family of transcription factors) is actively involved in the metabolism of many tumors, although the relationship between its expression levels and clinical significance in GC still need to be established. In this study, the level of HIF-1 alpha and NEDD4L mRNA and protein in 25 freshly frozen GC-and matched normal-tissues were determined by western blot and quantitative PCR (qPCR). Additionally, immunohistochemistry assay was performed to measure the protein level of NEDD4L and HIF-1 alpha in 124 GC and 25 normal control tissues. We observed that the NEDD4L mRNA and protein levels decreased significantly (P < 0.001) in GC tissues, while that of HIF-1 alpha increased (P < 0.001), and they both were associated with a poor prognosis, as was the case in patients with lower NEDD4L and higher HIF-1 alpha expression (P < 0.001). On correlation analysis, a significantly negative relationship (r = 0.288, P < 0.01) was revealed between NEDD4L and HIF-1 alpha expressions. Multivariate analysis revealed that co-expression of NEDD4L (P < 0.05) and HIF-1 alpha (P < 0.001) were independent predictors of GC prognosis. Thus, the correlation of NEDD4L and HIF-1 alpha levels may act as a prognostic marker of GC.