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Data Mining of Gene Arrays for Biomarkers of Survival in Ovarian Cancer

机译:卵巢癌生存生物标志物基因阵列的数据挖掘

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摘要

The expected five-year survival rate from a stage III ovarian cancer diagnosis is a mere 22%; this applies to the 7000 new cases diagnosed yearly in the UK. Stratification of patients with this heterogeneous disease, based on active molecular pathways, would aid a targeted treatment improving the prognosis for many cases. While hundreds of genes have been associated with ovarian cancer, few have yet been verified by peer research for clinical significance. Here, a meta-analysis approach was applied to two carefully selected gene expression microarray datasets. Artificial neural networks, Cox univariate survival analyses and T-tests identified genes whose expression was consistently and significantly associated with patient survival. The rigor of this experimental design increases confidence in the genes found to be of interest. A list of 56 genes were distilled from a potential 37,000 to be significantly related to survival in both datasets with a FDR of 1.39859 × 10−11, the identities of which both verify genes already implicated with this disease and provide novel genes and pathways to pursue. Further investigation and validation of these may lead to clinical insights and have potential to predict a patient’s response to treatment or be used as a novel target for therapy.
机译:Ⅲ期卵巢癌诊断的预期五年生存率仅为22%;这适用于英国每年诊断的7000例新病例。基于活跃的分子途径,将这种异质性疾病患者进行分层将有助于针对性治疗,从而改善许多病例的预后。尽管数百种基因与卵巢癌相关,但很少有同行研究证实其具有临床意义。在这里,荟萃分析方法应用于两个精心选择的基因表达微阵列数据集。人工神经网络,Cox单变量生存分析和T检验确定了其表达与患者生存一致且显着相关的基因。此实验设计的严格性提高了人们对发现感兴趣基因的信心。从潜在的37,000个数据集中提取出56个基因列表,这两个数据集的FDR为1.39859×10 −11 ,这两个数据集的身份验证了已经与该病相关的基因和提供新的基因和途径。对它们的进一步研究和验证可能会带来临床见解,并有可能预测患者对治疗的反应,或被用作治疗的新靶标。

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