基于TCGA数据库分析叉头盒蛋白FoxO1在 前列腺癌中的表达及其作用

目的：分析叉头盒蛋白FoxO1在前列腺癌（PCa）组织中的表达，探讨其对PCa早期诊断和预后的作用。方法：利用癌症基因图谱（TCGA）数据库下载正常前列腺组织和PCa组织中FoxO1 mRNA表达谱及临床信息资料，通过GEPIA数据库分析FoxO1mRNA表达与PCa临床病理学指标的关系及对预后的影响。采用Cox回归分析探讨PCa患者预后的影响因素。应用人类蛋白质表达图谱中的免疫组化结果分析FoxO1蛋白在正常前列腺组织和PCa组织中的表达情况。结果：与正常前列腺组织相比，FoxO1mRNA在PCa中表达降低（P<0.05），并且表达水平与肿瘤浸润深度、远处转移、分化程度存在相关关系（P均<0.05）。进一步研究发现FoxO1 mRNA高表达患者的无病生存率明显高于低表达患者（P<0.05）。Cox多因素分析结果表明，肿瘤浸润深度、分化程度和FoxO1表达水平是PCa患者预后的独立影响因素（P<0.05）。免疫组化结果显示，与正常前列腺组织相比，PCa中FoxO1的蛋白表达量亦显著降低（P<0.05）。结论：FoxO1基因在PCa组织中表达降低，其可能是一个抑癌基因，该基因的表达水平检测对前列腺癌患者的诊断和预后判断具有参考价值。

Utilizing the TCGA datasets to show clinical significance of FoxO1 expression in prostate cancers

OBJECTIVE:To investigate associations between expression of Forkhead box protein (FoxO1) and prognosis of prostate cancers (PCa). METHODS: FoxO1 expression data and the corresponding clinical data of PCa patients were downloaded from The Cancer Genome Atlas (TCGA). Expressions of FoxO1 mRNA in PCa tissues were measured by using the GEPIA database. Statistical analyses were performed for relationships between the expression and clinic-pathological factors and prognosis. Cox regression model was performed for the multivariate analysis. The Human Protein Atlas (HPA) was used to measure the UBE2C protein expression. RESULTS: Expression of FoxO1 mRNA was reduced in PCa compared to normal prostate tissues. The expression levels were correlated with the depth of tumor invasion, distant metastasis and degree of differentiation. The disease-free survival rates of patients with high FoxO1 expression were significantly higher than that of patients with low expression (P<0.05). Cox regression analyses show that the depth of tumor invasion and differentiation, and the expression of FoxO1 were independent prognostic factors for prostate cancers (P<0.05). Compared with the normal prostate tissues,immuno-histochemical staining show that FoxO1 expressions were significantly down-regulated in the PCa tissues (P<0.05). CONCLUSION:FoxO1 may be a tumor suppressor gene which can possibly provide the reference value for diagnosis and survival prognosis of patients with prostate cancer.