Unique volatolomic signatures of TP53 and KRAS in lung cells.

Unique volatolomic signatures of TP53 and KRAS in lung cells.
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DOI:
10.1038/bjc.2014.411
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发表时间:
2014-09-09
影响因子:
8.8
通讯作者:
Haick, H.
Haick, H.
中科院分区:
医学1区
文献类型:
--
作者:
Davies, M. P. A.;Barash, O.;Jeries, R.;Peled, N.;Ilouze, M.;Hyde, R.;Marcus, M. W.;Field, J. K.;Haick, H.

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挥发性有机化合物(VOC)是呼吸中癌症检测的潜在生物标志物,但尚不清楚它们是否反映了特定的突变。为了测试这一点,我们比较了携带KRASV 12突变、TP 53敲低或两者的人支气管上皮细胞(HBEC)细胞系与亲本HBEC细胞。通过被动采样收集培养细胞上方顶空中的VOC,并通过热解吸气相色谱-质谱(TD-GC-MS)或传感器阵列结合判别因子分析(DFA)进行分析。在TD-GC-MS分析中,单个化合物区分细胞系的能力有限,但通过应用20种VOC的DFA分析组合,成功区分了所有细胞类型(准确度为80- 100%,留一交叉验证)。传感器阵列检测DFA证明了基于细胞类型区分样品的能力,所有比较的准确度在77%和93%之间变化。我们的研究结果表明,支气管气道细胞中最小的遗传变化导致可检测的差异,通过TD-GC-MS或传感器阵列输出确定的模式的挥发性有机化合物的特定挥发性有机化合物的水平。从临床方面来看,这些结果表明,呼吸分析检测肺癌的早期诊断或基因分型的最小遗传变化的可能性。
Volatile organic compounds (VOCs) are potential biomarkers for cancer detection in breath, but it is unclear if they reflect specific mutations. To test this, we have compared human bronchial epithelial cell (HBEC) cell lines carrying the KRASV12 mutation, knockdown of TP53 or both with parental HBEC cells. VOC from headspace above cultured cells were collected by passive sampling and analysed by thermal desorption gas chromatography mass spectrometry (TD-GC–MS) or sensor array with discriminant factor analysis (DFA). In TD-GC–MS analysis, individual compounds had limited ability to discriminate between cell lines, but by applying DFA analysis combinations of 20 VOCs successfully discriminated between all cell types (accuracies 80–100%, with leave-one-out cross validation). Sensor array detection DFA demonstrated the ability to discriminate samples based on their cell type for all comparisons with accuracies varying between 77% and 93%. Our results demonstrate that minimal genetic changes in bronchial airway cells lead to detectable differences in levels of specific VOCs identified by TD-GC–MS or of patterns of VOCs identified by sensor array output. From the clinical aspect, these results suggest the possibility of breath analysis for detection of minimal genetic changes for earlier diagnosis or for genetic typing of lung cancers.
使用比色法传感器阵列进行呼气呼吸分析,以鉴定和表征肺癌。
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