文章题目：A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma
文章链接：https://www.nature.com/articles/ncomms9699?origin=ppub
目的
简而言之we develop and validate a practical and reliable classifier based on genome-wide CpG methylation profiling that improves risk stratification for patients with ccRCC.
流程图
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结果
结果一
Identifying candidate CpGs based on genome-wide profiling.
analysed 46 paired ccRCC and adjacent normal tissues by CpG methylation microarray (Infinium HumanMethylation450 array)
火山图找甲基化位点102个，log2 fold change >2.5
The 102 CpGs identified in univariate analysis were entered into a multivariate logistic regression model (the least absolute shrinkage and selection operator (LASSO)) and 18 had non-zero coefficients
从单因素102个甲基化位点到多因素逻辑回归（lasso）确定了18个non-zero coefficients
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结果二
Constructing and validating the CpG-based classifier.
multivariate LASSO Cox regression model to build a CpG-based prognostic classifier, which included 5 of the 18 CpGs: cg00396667, cg18815943, cg03890877, cg07611000 and cg14391855 (Fig. 2d）
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四个数据集做验证
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The patients were divided into low-risk and high-risk groups using the median cutoff value of the classifier risk score ( 0.1).
结果三
Stratification analysis of the five-CpG-based classifier.
关于分层之前写过一篇文献抄读：几篇 CpG的文献阅读里面写过对于分层的概念不是很懂，不过现在可以懂了，这篇文献中描述了
Survival analysis was further performed with regard to the five-CpG-based classifier in subsets of patients with different clinical variables. When stratified by clinical variables (sex, age, race, Fuhrman grade, tumour size and necrosis status), the five-CpG-based classifier was still a clinically and statistically significant prognostic model.
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相同临床分期的人同样可以分为高低风险组并且有高低预后的区分
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另外根据 SSIGN score是ccRcc的一种临床整合系统，用来评估这个five -classifier 的准确性，可以将病人不同SSIGN score的成功分为高、低风险组
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结果四
Impact of intratumour heterogeneity.
intratumour heterogeneity 肿瘤内异质性是否受分类器的影响
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结果五
CpG methylation and gene expression and patient prognosis.
下面的描述没有图片
疑惑1：几种完全不相关、相关的PITX1的是4.1x10-8，可是明明小于前面说的significantly inverse的EHBP1L1啊
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疑惑2：连着上面的疑惑1:红色代表marker expresson与生存不相关，可是看着挺相关的呀
疑惑3:X-tile plots provide a single and intuitive method to assess the association between marker expression and survival, and automatically select the optimum cut point according to the highest w2-value defined by Kaplan–Meier survival analysis and log-rank test. Colouration of the plot represents the strength of the association at each division, ranging from low (dark, black) to high (bright, red or green) 还是图注和图片无法对应上。
结果六
Integrating our results with genes linked to RCC
用的cBioPortal for Cancer Genomics network to evaluate gene con- nectivity.
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