文章題目
響應(yīng)老大生信菜鳥團(tuán)推文:一起來看文獻(xiàn)吧!
本次閱讀文獻(xiàn)題目: Five-DNA methylation signature act as anovel prognostic biomarker in patientswith ovarian serous cystadenocarcinoma.
生詞
hypermethylation 高甲基化
hypomethylation 低甲基化
目的
The potential clinical significance of methyla-tion biomarkers serving as molecular prognostic markerswas examined using Kaplan–Meier method and receiveroperating characteristic (ROC) analysis.
結(jié)果
結(jié)果一
Identification of DNA methylation markers associatedwith the OS of patients in the training dataset
單因素cox回歸:找到 1630 DNA methylation sites (P< 0.05)
多因素cox回歸:找到5個甲基化味道 (cg05254747, cg13652336,cg25123470, cg06038133, and cg04907664)
這5個被認(rèn)為是預(yù)測病人生存期的最佳標(biāo)記闽铐。
同時文章有下面一段描述疏橄,是關(guān)于risk score的
在《基于TCGA數(shù)據(jù)庫篩選乳腺癌不良預(yù)后相關(guān)mi+RNAs及風(fēng)險評估》也看到過占拍,描述如下:
我們使用R,使用Survival程序包的Predict函數(shù)捎迫,根據(jù)公式風(fēng)險評分 =h0(t)(Exp miRNA1* βmiRNA1+...... +ExpmiRNAn*βmiRNAn)計算出每位患者的風(fēng)險評分晃酒,以 風(fēng)險評分的中位值將患者分為兩組,大于中位值的患者為高風(fēng)險組窄绒,小于或等于中位值的患者為低風(fēng) 險組贝次。
計算如下圖:存活風(fēng)險評分(SRS)
現(xiàn)在我的疑問是這個值是哪來的,應(yīng)該就是Survival程序包的Predict函數(shù)得來的彰导,需要后面碰到再繼續(xù)浊闪。
關(guān)于單因素和多因素cox回歸恼布,如下描述
好了,下面這個就讓我明白了搁宾,那么就是這個AUC到底是什么作用了,不是從萬千叢中挑選了幾只嘛倔幼,那么是根據(jù)什么挑選的呢盖腿?下面是Materials and methods的描述:
Subsequently, AUC wasused to measure and compare the model performance;the model with a higher predictive performance was eventually selected out. The model could be used to construct a risk score formula that would be helpful topredict survival. The prognostic risk scores for each pa-tient were calculated based on this formula. According to their prognostic risk scores, these patients were ranked and further separated into“l(fā)ow-risk”and“high--risk”groups using the median risk score as the cutoff point. Patients with risk score higher than the medianrisk score were assigned to the high-risk group, whereas patients with lower risk were assigned to the low-risk group. After that, the Kaplan–Meier estimator, a non-parametric statistic, with log-rank test (Mantel–Cox)was used to calculate the cumulative survival time and compare the differences in OS between the two groups.Kaplan–Meier curves were drawn using the“survival”package.
總結(jié)上面就是,根據(jù)AUC的值來選擇模型损同,哪些基因組成的AUC值最高翩腐,那些基因組成的那個模型就是最好的。然后用這個模型膏燃。然后對這個模型進(jìn)行一個風(fēng)險評分茂卦。接下來根據(jù)預(yù)后分險評分,用median risk score將病人分為高低風(fēng)險組组哩。接下來用Kaplan–Meier(“survival”包)來對剛剛分出來的高低風(fēng)險組進(jìn)行一個生存分析的預(yù)測等龙,從而來判斷這個模型是否合格。
結(jié)果二
Association between five-DNA methylation signature andpatient OS in the training and validation datasets
上面的cox回歸伶贰,通過Hazard ratios (HRs)可以說明這個five-DNA methylation與病人生存相關(guān)蛛砰。
Hazard ratios (HRs) from the Cox regression analysis indi-cated that the five-DNA methylation signature was signifi-cantly associated with the OS of patients (P<0.001, HR2.72, 95% CI 2.03–3.65).
用 Kaplan–Meier analysis 來評價這個新建立的five-DNA methylation的效能
The Kaplan–Meier analysis wasperformed in the training and validation datasets to deter-mine the potential predictive value of this five-DNA methylation signature in the prognosis.
上面的截圖說明這個five-DNA methylation could distinguish high-risk patients fromlow-risk patients, implying its significance in theprognostic prediction of OSC.
同時,高低風(fēng)險組的這個5個甲基化位點的高低也進(jìn)行了分析:
high-risk patients exhibited signifi-cantly lower methylation levels for cg05254747 andcg04907664 and significantly higher methylation levelsfor the other three methylation sites in both training
結(jié)果三
Evaluation of the predictive performance of the five-DNA methylation signature using ROC analysis
利用ROC分析評估five-DNA methylation特征在預(yù)測生存中的敏感性和特異性黍衙,進(jìn)一步評估評估數(shù)據(jù)集中five-DNA methylation特征的預(yù)測準(zhǔn)確性泥畅。five-DNA methylation 特征的AUC為0.715 (P< 0.001, 95% CI 0.62-0.81)(圖2),表明five-DNA methylation具有較高的敏感性和特異性琅翻。因此位仁,該方法可用于預(yù)測OSC患者的預(yù)后生存期,具有較高的準(zhǔn)確性方椎,在臨床應(yīng)用中可能具有重要的意義聂抢。
結(jié)果四
Predictive performance of the five-DNA methylationsignature based on different regrouping methods
由于預(yù)后相關(guān)因素有很多,比如 age, stag, histologicgrade, and size of residual tumor after cytoreductivesurgery, and the reproducibility was poor in the prog-nostic markers identified by different groups等辩尊。
作者用三個年齡段(小于50涛浙、51-60、大于61)的高低風(fēng)險組摄欲,來看生存時間轿亮,并且給出了ROC曲線,也就可以看到AUC值胸墙。三個年齡段的高低風(fēng)險組我注,均具有顯著差異,下面只展示第一張結(jié)果圖迟隅。
接下來 作者把其他與生存相關(guān)的臨床信息進(jìn)行了以表格形式的展示但骨,來證明他們這個ive-DNA methylation的棒棒励七!
結(jié)果五
Comparison of the five-DNA methylation signature withother known prognostic biomarkers
將本文中的five-DNA methylation與其他文章研究中biomarker進(jìn)行比較,得到下面的圖奔缠,同樣是通過AUC值的高低來判斷誰最棒掠抬,可見five-DNA methylation是最棒的。
總結(jié)
通過結(jié)果可以了解作者這篇生存分析的思路校哎,是我最大的收獲两波!