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Journal of ZheJiang University (Engineering Science)  2019, Vol. 53 Issue (12): 2389-2395    DOI: 10.3785/j.issn.1008-973X.2019.12.017
Computer Science and Artificial Intelligence     
Screening and bioinformatics analysis of lung cancer exhale breath biomarkers
Qian WU(),Ping WANG*()
Key Laboratory for Biomedical Engineering of Education Ministry, Zhejiang University, Hangzhou 310027, China
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Abstract  

The exhale breath detection combined bioinformatics analysis method, including transcriptome, metabolic pathway and protein structure, was proposed to identify gas markers for screening and diagnosis of lung cancer. Lung cancer patients and healthy controls' samples were collected to performe GC-MS and ROC curve analysis which obtained ten specific VOCs. Differentially expressed genes were obtained by transcriptome analysis. The differentially expressed genes and relative metabolic pathways were consistent with in vivo biological process, which meant that these VOCs come from the metabolism of lung cancer patient. The sensitivity, specificity and overall accuracy of lung cancer diagnosis model established based on VOCs were 86.2%, 91.2% and 89.6%, respectively. Thus, the proposed method can distinguish normal people and lung cancer patients simply and effectively, providing convenient approach for early screening of lung cancer.



Key wordsexhale breath detection      lung cancer biomarker      bioinformatics      transcriptome analysis      protein structure analysis      early screening of lung cancer     
Received: 03 October 2018      Published: 17 December 2019
CLC:  R 318  
Corresponding Authors: Ping WANG     E-mail: qianwu@zju.edu.cn;cnpwang@zju.edu.cn
Cite this article:

Qian WU,Ping WANG. Screening and bioinformatics analysis of lung cancer exhale breath biomarkers. Journal of ZheJiang University (Engineering Science), 2019, 53(12): 2389-2395.

URL:

http://www.zjujournals.com/eng/10.3785/j.issn.1008-973X.2019.12.017     OR     http://www.zjujournals.com/eng/Y2019/V53/I12/2389


肺癌呼吸标志物筛选及其生物信息学分析

采用结合转录组、代谢通路、蛋白结构的呼出气体检测生物信息学分析方法来确定肺癌气体标志物,用于肺癌的筛选诊断. 采用标准仪器(GCMS)检测肺癌病人和正常人的呼吸气体样本;经统计分析,筛选出10种特异性挥发性有机物(VOC). 采用转录组分析得到肺癌和健康人的差异表达基因,其富集的代谢通路与人体内产生VOC的代谢通路一致,证明所筛选的VOC标志物与肺癌病人代谢具有相关性. 基于此VOC建立的肺癌诊断模型的灵敏度、特异性和整体正确率分别为86.2%,91.2% 和89.6%,说明所提方法能简便、有效区分正常人和肺癌病人,为早期肺癌筛查提供方便、可靠的检测方法.


关键词: 呼出气体检测,  肺癌标志物,  生物信息学,  转录组分析,  蛋白结构分析,  肺癌早期筛查 
临床信息 肺癌实验组人数 健康对照组人数
性别 39 76
19 49
吸烟状况 吸烟 22 47
戒烟 8 18
非吸烟 28 60
肺癌类型 腺癌 29 ?
鳞癌 26 ?
大细胞癌 0 ?
小细胞癌 3 ?
非小细胞癌分期 I 10 ?
II 6 ?
III 11 ?
IV 28 ?
小细胞癌分期 局限期 0 ?
广泛期 3 ?
Tab.1 Statistic of basic clinical information of subjects
Fig.1 Collection and analysis of subjects’ exhale breath
金标准 测试结果
阴性 阳性
注:假阳性率=B/(A+B),特异度=1?假阳性率;真阳性率=D/(C+D),灵敏度=真阳性率
阴性 真阴性(A) 假阳性(B)
阳性 假阴性(C) 真阳性(D)
Tab.2 Logistic regression method for dichotomous classification
VOCs AUCs P 95%置信区间
下限 上限
3-乙基甲苯 0.882 <0.001 0.827 0.936
1,2,3-三甲苯 0.876 <0.001 0.825 0.928
丙基苯 0.842 <0.001 0.783 0.902
正丙基环己烷 0.840 <0.001 0.780 0.900
茚满 0.801 <0.001 0.737 0.865
1-甲基-3-丙基苯 0.800 <0.001 0.734 0.865
邻二甲苯 0.773 <0.001 0.707 0.839
4-甲基-2-戊酮 0.763 <0.001 0.687 0.839
正己醛 0.758 <0.001 0.686 0.830
甲基环己烷 0.753 <0.001 0.681 0.825
Tab.3 Analysis results of lung cancer specific volatile organic compound (VOC)
Fig.2 Venn diagram of differentially-expressed genes computed through edgeR and DESeq
VOCs 类别 代谢过程 关键酶
正丙基环己烷
甲基环己烷
烷烃类 氧化应激反应 细胞色素p450
4-甲基-2-戊酮
正己醛
醛酮类 脂质过氧化反应
脱氢作用
细胞色素p450
醇脱氢酶
3-乙基甲苯
1,2,3-三甲苯
丙基苯
茚满
1-甲基-3-丙基苯
邻二甲苯
烷基苯 自身免疫防御 细胞色素p450
谷胱甘肽S转移酶
磺基转移酶
乙酰转移酶
Tab.4 Metabolic pathways and key enzymes that produce VOC in human body
Fig.3 Protein structure of ALDH1A3
Fig.4 Space collision of Lys411 with NAD and Phe413 in mutated ALDH1A3
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