DDX3X Biomarker Correlates with Poor Survival in Human Gliomas.
DDX3X Biomarker Correlates with Poor Survival in Human Gliomas.
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DOI：
10.3390/ijms160715578
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发表时间：
2015-07-09
影响因子：
5.6
通讯作者：
Lin MH
中科院分区：
文献类型：
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作者：
Hueng DY;Tsai WC;Chiou HY;Feng SW;Lin C;Li YF;Huang LC;Lin MH
原发性高级别胶质瘤具有侵袭性生长，导致不良的生存结果。研究胶质瘤患者生存预后的生物标志物对临床评估具有重要意义。DEAD （Asp-Glu-Ala-Asp）盒解旋酶3，X-linked （DDX3X）控制肿瘤的迁移、增殖和进展。然而，DDX3X在确定胶质瘤患者病理分级和生存结局中的作用尚不清楚。我们分析了DDX3X基因表达、WHO病理分级和去关联数据的总生存率。利用正常脑和胶质瘤cDNA的定量RT-PCR和组织芯片的免疫组化（IHC）染色进一步验证。GEO数据集的统计分析显示，DDX3X mRNA在WHOⅳ级患者中的表达（n = 81）高于非肿瘤对照组（n = 23, p = 1.13 × 10−10）。此外，WHO III级患者（n = 19）的DDX3X水平也高于非肿瘤对照组（p = 2.43 × 10−5）。Kaplan-Meier生存分析显示，DDX3X mRNA表达水平高的患者（n = 24）比DDX3X mRNA表达水平低的患者（n = 53）的生存率低（中位生存期，115周vs. 58周，p = 0.0009， log-rank检验，风险比：0.3507,95% CI: 0.1893-0.6496）。此外，通过定量RT-PCR和Western blot检测，与正常脑组织相比，胶质瘤细胞中DDX3X mRNA的表达和蛋白的产生显著增加。与正常脑组织相比，免疫组化染色显示高度胶质瘤。综上所述，DDX3X表达水平与WHO病理分级和不良生存结果呈正相关，表明DDX3X是人类胶质瘤中有价值的生物标志物。
Primary high-grade gliomas possess invasive growth and lead to unfavorable survival outcome. The investigation of biomarkers for prediction of survival outcome in patients with gliomas is important for clinical assessment. The DEAD (Asp-Glu-Ala-Asp) box helicase 3, X-linked (DDX3X) controls tumor migration, proliferation, and progression. However, the role of DDX3X in defining the pathological grading and survival outcome in patients with human gliomas is not yet clarified. We analyzed the DDX3X gene expression, WHO pathological grading, and overall survival from de-linked data. Further validation was done using quantitative RT-PCR of cDNA from normal brain and glioma, and immunohistochemical (IHC) staining of tissue microarray. Statistical analysis of GEO datasets showed that DDX3X mRNA expression demonstrated statistically higher in WHO grade IV (n = 81) than in non-tumor controls (n = 23, p = 1.13 × 10−10). Moreover, DDX3X level was also higher in WHO grade III (n = 19) than in non-tumor controls (p = 2.43 × 10−5). Kaplan–Meier survival analysis showed poor survival in patients with high DDX3X mRNA levels (n = 24) than in those with low DDX3X expression (n = 53) (median survival, 115 vs. 58 weeks, p = 0.0009, by log-rank test, hazard ratio: 0.3507, 95% CI: 0.1893–0.6496). Furthermore, DDX3X mRNA expression and protein production significantly increased in glioma cells compared with normal brain tissue examined by quantitative RT-PCR, and Western blot. IHC staining showed highly staining of high-grade glioma in comparison with normal brain tissue. Taken together, DDX3X expression level positively correlates with WHO pathologic grading and poor survival outcome, indicating that DDX3X is a valuable biomarker in human gliomas.