Detecting Liver Cancer Using Cell-Free DNA Fragmentomes.
Detecting Liver Cancer Using Cell-Free DNA Fragmentomes.
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DOI：
10.1158/2159-8290.cd-22-0659
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发表时间：
2023-03-01
期刊：
影响因子：
28.2
通讯作者：
中科院分区：
文献类型：
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作者：
使用来自全基因组无细胞DNA分析的多特征片段组数据的机器学习模型在平均和高风险人群（包括早期疾病）中以高灵敏度和特异性检测肝细胞癌。肝癌是全世界癌症死亡的主要原因。筛查高危人群，包括肝硬化和病毒性肝炎患者，为提高生存率提供了一条途径，但目前的筛查方法还不充分。在这项研究中，我们使用全基因组无细胞DNA （cfDNA）片段组分析来评估来自美国、欧盟或香港的724例肝细胞癌（HCC）患者或HCC平均或高风险患者。使用结合多特征片段组数据的机器学习模型，检测癌症的灵敏度在平均风险人群中为88%，特异性为98%，在高风险人群中为85%，特异性为80%。我们在独立人群中验证了这些结果。cfDNA片段化变化反映了肝癌中基因组和染色质的变化，包括转录因子结合位点的变化。这些发现为肝癌患者cfDNA片段的变化提供了生物学基础，并为非侵入性癌症检测提供了一种可行的方法。在世界范围内，对简便、灵敏的HCC筛查方法有很大的需求。我们已经开发了一种检测全基因组cfDNA片段特征的方法，为肝癌检测提供了一种高效、经济的方法。见相关评论罗尔夫和罗素，第532页。这篇文章在本期特刊第517页突出显示
A machine learning model using multifeature fragmentome data from genome-wide cell-free DNA analyses detected hepatocellular carcinoma with high sensitivity and specificity in average and high-risk populations, including in early-stage disease. Liver cancer is a major cause of cancer mortality worldwide. Screening individuals at high risk, including those with cirrhosis and viral hepatitis, provides an avenue for improved survival, but current screening methods are inadequate. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome analyses to evaluate 724 individuals from the United States, the European Union, or Hong Kong with hepatocellular carcinoma (HCC) or who were at average or high-risk for HCC. Using a machine learning model that incorporated multifeature fragmentome data, the sensitivity for detecting cancer was 88% in an average-risk population at 98% specificity and 85% among high-risk individuals at 80% specificity. We validated these results in an independent population. cfDNA fragmentation changes reflected genomic and chromatin changes in liver cancer, including from transcription factor binding sites. These findings provide a biological basis for changes in cfDNA fragmentation in patients with liver cancer and provide an accessible approach for noninvasive cancer detection. There is a great need for accessible and sensitive screening approaches for HCC worldwide. We have developed an approach for examining genome-wide cfDNA fragmentation features to provide a high-performing and cost-effective approach for liver cancer detection. See related commentary Rolfo and Russo, p. 532. This article is highlighted in the In This Issue feature, p. 517
DOI：
10.5402/2012/421673
发表时间：
2012
期刊：
ISRN oncology
影响因子：
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作者：
Waly Raphael S;Yangde Z;Yuxiang C
通讯作者：
Yuxiang C