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Microbiome analyses of blood and tissues suggest cancer diagnostic approach.

血液和组织的微生物组分析提示癌症诊断方法。

  • 影响因子:15.21
  • DOI:10.1038/s41586-020-2095-1
  • 作者列表:"Poore GD","Kopylova E","Zhu Q","Carpenter C","Fraraccio S","Wandro S","Kosciolek T","Janssen S","Metcalf J","Song SJ","Kanbar J","Miller-Montgomery S","Heaton R","Mckay R","Patel SP","Swafford AD","Knight R
  • 发表时间:2020-03-01
Abstract

:Systematic characterization of the cancer microbiome provides the opportunity to develop techniques that exploit non-human, microorganism-derived molecules in the diagnosis of a major human disease. Following recent demonstrations that some types of cancer show substantial microbial contributions1-10, we re-examined whole-genome and whole-transcriptome sequencing studies in The Cancer Genome Atlas11 (TCGA) of 33 types of cancer from treatment-naive patients (a total of 18,116 samples) for microbial reads, and found unique microbial signatures in tissue and blood within and between most major types of cancer. These TCGA blood signatures remained predictive when applied to patients with stage Ia-IIc cancer and cancers lacking any genomic alterations currently measured on two commercial-grade cell-free tumour DNA platforms, despite the use of very stringent decontamination analyses that discarded up to 92.3% of total sequence data. In addition, we could discriminate among samples from healthy, cancer-free individuals (n = 69) and those from patients with multiple types of cancer (prostate, lung, and melanoma; 100 samples in total) solely using plasma-derived, cell-free microbial nucleic acids. This potential microbiome-based oncology diagnostic tool warrants further exploration.

摘要

: 癌症微生物组的系统表征提供了开发利用非人类、微生物来源的分子诊断主要人类疾病的技术的机会。在最近证明某些类型的癌症显示出大量微生物contributions1-10 后,我们重新研究了癌症基因组Atlas11 (TCGA) 中的全基因组和全转录组测序研究在来自未经治疗的患者的 33 种癌症 (共 18,116 个样本) 的微生物读数中,并在大多数主要类型的癌症内部和之间的组织和血液中发现了独特的微生物特征。这些TCGA血液特征在应用于Ia-IIc期癌症和目前在两个商业级无细胞肿瘤DNA平台上测量的缺乏任何基因组改变的癌症患者时仍然具有预测性,尽管使用了非常严格的去污分析,丢弃了高达 92.3% 的总序列数据。此外,我们可以区分来自健康的无癌个体 (n = 69) 和来自多种类型癌症 (前列腺癌,肺癌和黑色素瘤) 患者的样本; 总共 100 个样品) 仅使用血浆来源的无细胞微生物核酸。这种潜在的基于微生物组的肿瘤学诊断工具值得进一步探索。

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影响因子:6.93
发表时间:2020-01-15
DOI:10.1002/ijc.32532
作者列表:["Hata A","Nakajima T","Matsusaka K","Fukuyo M","Morimoto J","Yamamoto T","Sakairi Y","Rahmutulla B","Ota S","Wada H","Suzuki H","Matsubara H","Yoshino I","Kaneda A"]

METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.

翻译标题与摘要 下载文献
影响因子:6.93
发表时间:2020-01-01
DOI:10.1002/ijc.32530
作者列表:["Zhang L","Yang Y","Chai L","Bu H","Yang Y","Huang H","Ran J","Zhu Y","Li L","Chen F","Li W"]

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肺肿瘤方向

肺肿瘤,又叫支气管肺癌,是常见的恶性肿瘤之一。肺肿瘤的治疗为包括手术、中药、放疗、化疗及免疫等多学科的综合治疗。

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