A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C
A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C
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DOI：
10.1002/hep.21695
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发表时间：
2007-08-01
期刊：
影响因子：
13.5
通讯作者：
Cheung, Ramsey C.
中科院分区：
文献类型：
--
作者：
Huang, Honjin;Shiffman, Mitchefl L.;Cheung, Ramsey C.
临床因素如年龄、性别、酒精使用和感染年龄影响肝硬化的进展，但不能准确预测慢性丙型肝炎（CHC）患者发生肝硬化的风险。本研究的目的是为白种人肝硬化患者开发一种预测特征。所有患者均具有良好的肝脏组织学特征和临床因素；从全血中提取DNA进行基因分型。我们在训练队列中验证了基因组扫描中所有重要的标记，并选择了361个标记用于签名构建。使用“机器学习”方法，在训练集（N = 420）中开发了一个由最能预测高加索患者肝硬化风险的标志物组成的签名。计算肝硬化风险评分（CRS）来估计每位患者发生肝硬化的风险。然后在154名高加索患者的独立注册验证队列中测试CRS的性能。由7个标记组成的CRS特征被用于高加索患者。训练组CRS的roc曲线下面积（AUC）为0.75。在验证队列中，临床因素的AUC仅为0.53，CRS的AUC为0.73，CRS和临床因素联合的AUC为0.76。以< 0.50的低CRS截断值识别低危患者时，仅有10.3%的高危患者误分类，而以< 0.70的高CRS截断值识别高风险患者时，有22.3%的低危患者误分类。结论：与临床因素相比，CRS是区分高加索CHC患者肝硬化高危与低危的更好预测指标。应该进行前瞻性研究以进一步验证这些发现。
Clinical factors such as age, gender, alcohol use, and age-at-infection influence the progression to cirrhosis but cannot accurately predict the risk of developing cirrhosis in patients with chronic hepatitis C (CHC). The aim of this study was to develop a predictive signature for cirrhosis in Caucasian patients. All patients had well-characterized liver histology and clinical factors; DNA was extracted from whole blood for genotyping. We validated all significant markers from a genome scan in the training cohort, and selected 361 markers for the signature building. Using a "machine learning" approach, a signature consisting of markers most predictive for cirrhosis risk in Caucasian patients was developed in the training set (N = 420). The Cirrhosis Risk Score (CRS) was calculated to estimate the risk of developing cirrhosis for each patient. The CRS performance was then tested in an independently enrolled validation cohort of 154 Caucasian patients. A CRS signature consisting of 7 markers was developed for Caucasian patients. The area-under-the-ROC curves (AUC) of the CRS was 0.75 in the training cohort. In the validation cohort, AUC was only 0.53 for clinical factors, increased to 0.73 for CRS, and 0.76 when CRS and clinical factors were combined. A low CRS cutoff of < 0.50 to identify low-risk patients would misclassify only 10.3% of high-risk patients, while a high cutoff of > 0.70 to identify high-risk patients would misclassify 22.3% of low-risk patients. Conclusion: CRS is a better predictor than clinical factors in differentiating high-risk versus low-risk for cirrhosis in Caucasian CHC patients. Prospective studies should be conducted to further validate these findings.