Cancer type classification using plasma cell-free RNAs derived from human and microbes.
Cancer type classification using plasma cell-free RNAs derived from human and microbes.
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使用来自人类和微生物的血浆无细胞RNA进行癌症类型分类。
DOI：
10.7554/elife.75181
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发表时间：
2022-07-11
期刊：
影响因子：
7.7
通讯作者：
Wang, Pengyuan
中科院分区：
文献类型：
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作者：
Chen, Shanwen;Jin, Yunfan;Wang, Siqi;Xing, Shaozhen;Wu, Yingchao;Tao, Yuhuan;Ma, Yongchen;Zuo, Shuai;Liu, Xiaofan;Hu, Yichen;Chen, Hongyan;Luo, Yuandeng;Xia, Feng;Xie, Chuanming;Yin, Jianhua;Wang, Xin;Liu, Zhihua;Zhang, Ning;Zech Xu, Zhenjiang;Lu, Zhi John;Wang, Pengyuan
无细胞核酸在监测癌症方面的实用性已得到科学家和临床医生的认可。除了人类转录物之外，人类血浆中的一部分无细胞核酸被证明来源于微生物，并被报道与癌症相关。为了更好地了解癌症患者中的血浆无细胞RNA（cfRNA），我们用RNA-seq分析了5种癌症类型（结直肠癌、胃癌、肝癌、肺癌和食管癌）和健康供体（HD）的约300个血浆样品中的cfRNA。当仔细过滤潜在的污染物时，通过不同的计算方法一致地检测到微生物来源的cfRNA。从人类和微生物读数中鉴定了临床相关信号，并且下调的人类基因和更高流行率的细环扭病毒的丰富的京都基因和基因组百科全书途径都表明一部分癌症患者是免疫抑制的。我们的数据支持人和微生物来源的血浆cfRNA用于癌症检测的诊断价值，因为实现了用于区分癌症患者与HD的约0.9的ROC曲线下面积。此外，人类和微生物cfRNA都具有癌症类型特异性，结合两种类型的特征可以区分五种不同原发部位的肿瘤，平均召回率为60.4%。与单独使用人类特征相比，添加微生物特征使平均召回率提高了约8%。总之，这项工作为人和微生物来源的血浆cfRNA的临床相关性及其在癌症检测以及肿瘤部位确定中的潜在效用提供了证据。
The utility of cell-free nucleic acids in monitoring cancer has been recognized by both scientists and clinicians. In addition to human transcripts, a fraction of cell-free nucleic acids in human plasma were proven to be derived from microbes and reported to have relevance to cancer. To obtain a better understanding of plasma cell-free RNAs (cfRNAs) in cancer patients, we profiled cfRNAs in ~300 plasma samples of 5 cancer types (colorectal cancer, stomach cancer, liver cancer, lung cancer, and esophageal cancer) and healthy donors (HDs) with RNA-seq. Microbe-derived cfRNAs were consistently detected by different computational methods when potential contaminations were carefully filtered. Clinically relevant signals were identified from human and microbial reads, and enriched Kyoto Encyclopedia of Genes and Genomes pathways of downregulated human genes and higher prevalence torque teno viruses both suggest that a fraction of cancer patients were immunosuppressed. Our data support the diagnostic value of human and microbe-derived plasma cfRNAs for cancer detection, as an area under the ROC curve of approximately 0.9 for distinguishing cancer patients from HDs was achieved. Moreover, human and microbial cfRNAs both have cancer type specificity, and combining two types of features could distinguish tumors of five different primary locations with an average recall of 60.4%. Compared to using human features alone, adding microbial features improved the average recall by approximately 8%. In summary, this work provides evidence for the clinical relevance of human and microbe-derived plasma cfRNAs and their potential utilities in cancer detection as well as the determination of tumor sites.