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肺癌患者淋巴细胞中的遗传损伤与呼吸道微生物组的组成有关。

Genetic damage in lymphocytes of lung cancer patients is correlated to the composition of the respiratory tract microbiome.

机构信息

Kemerovo State University, Kemerovo, Russian Federation, Krasnaya St., 6.

Institute of Living Systems, Immanuel Kant Baltic Federal University, Kaliningrad, Russian Federation, Kaliningrad, st. A. Nevsky, 14.

出版信息

Mutagenesis. 2021 May 31;36(2):143-153. doi: 10.1093/mutage/geab004.

DOI:10.1093/mutage/geab004
PMID:33454779
Abstract

Recent findings indicate that the microbiome may have significant impact on the development of lung cancer by its effects on inflammation, dysbiosis or genome damage. The aim of this study was to compare the sputum microbiome of lung cancer (LC) patients with the chromosomal aberration (CA) and micronuclei (MN) frequency in peripheral blood lymphocytes. In the study, the taxonomic composition of the sputum microbiome of 66 men with untreated LC were compared with 62 control subjects with respect to CA and MN frequency and centromere fluorescence in situ hybridisation analysis. Results showed a significant increase in CA (4.11 ± 2.48% versus 2.08 ± 1.18%) and MN (1.53 ± 0.67% versus 0.87 ± 0.49%) frequencies, respectively, in LC patients as compared to control subjects. The higher frequency of centromeric positive MN of LC patients was mainly due to aneuploidy. A significant increase in Streptococcus, Bacillus, Gemella and Haemophilus in LC patients was detected, in comparison to the control subjects while 18 bacterial genera were significantly reduced, which indicates a decrease in the beta diversity in the microbiome of LC patients. Although, the CA frequency in LC patients is significantly associated with an increased presence of the genera Bacteroides, Lachnoanaerobaculum, Porphyromonas, Mycoplasma and Fusobacterium in their sputum, and a decrease for the genus Granulicatella after application of false discovery rate correction, significance was not any more present. The decrease of MN frequency of LC patients is significantly associated with an increase in Megasphaera genera and Selenomonas bovis. In conclusion, a significant difference in beta diversity of microbiome between LC and control subjects and association between the sputum microbiome composition and genome damage of LC patients was detected, thus supporting previous studies suggesting an etiological connection between the airway microbiome and LC.

摘要

最近的研究结果表明,微生物组通过对炎症、失调或基因组损伤的影响,可能对肺癌的发生发展产生重大影响。本研究旨在比较肺癌(LC)患者的痰液微生物组与外周血淋巴细胞的染色体畸变(CA)和微核(MN)频率。在这项研究中,我们比较了 66 名未经治疗的 LC 男性患者和 62 名对照者的痰液微生物组的分类组成,比较了 CA 和 MN 频率以及着丝粒荧光原位杂交分析。结果显示,与对照组相比,LC 患者的 CA(4.11 ± 2.48%比 2.08 ± 1.18%)和 MN(1.53 ± 0.67%比 0.87 ± 0.49%)频率显著升高。LC 患者的着丝粒阳性 MN 频率较高主要是由于非整倍体。与对照组相比,LC 患者的链球菌、芽孢杆菌、孪生菌和嗜血杆菌显著增加,而 18 个细菌属显著减少,这表明 LC 患者的微生物组β多样性减少。尽管 LC 患者的 CA 频率与痰中细菌属的存在显著相关,如拟杆菌属、lachnoanaerobaculum 属、卟啉单胞菌属、支原体属和梭杆菌属的增加,以及颗粒杆菌属的减少,但在应用错误发现率校正后,其相关性不再显著。LC 患者 MN 频率的降低与 megasphaera 属和 Selenomonas bovis 的增加显著相关。总之,我们发现 LC 患者和对照组之间的微生物组β多样性存在显著差异,以及 LC 患者的痰液微生物组组成与基因组损伤之间存在关联,这支持了先前的研究结果,表明气道微生物组与 LC 之间存在病因联系。

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