A Multi-Omics Study of Familial Lung Cancer: Microbiome and Host Gene Expression Patterns.
A Multi-Omics Study of Familial Lung Cancer: Microbiome and Host Gene Expression Patterns.
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DOI：
10.3389/fimmu.2022.827953
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发表时间：
2022
影响因子：
7.3
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中科院分区：
文献类型：
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遗传易感性和环境致癌物是肺癌病因学的关键因素。肺部微生物群在致癌作用中越来越受到关注。目前的工作旨在研究受家族性肺癌（FLC）和室内空气污染（IAP）影响的肺癌患者的微生物组；进一步，比较宿主基因表达模式与其微生物组的潜在联系。组织样本对（癌症和邻近的非恶性组织）用于 16S rRNA（微生物组）和 RNA-seq（宿主基因表达）。分析了亚组微生物组多样性及其匹配的基因表达模式。根据不同的临床病理特征筛选出显着丰富的类群。我们的 FLC 微生物组似乎更小、多样性低且不积极改变；我们注意到微生物组在性别、年龄、血型、解剖部位、组织学类型、TNM 分期以及 IAP 和吸烟条件方面的差异。我们还发现吸烟和 IAP 显着降低了特定 OTU 的生物多样性，尤其是在正常肺组织中。有趣的是，富集的微生物分为三类：机会病原体、益生菌和污染物解毒微生物；第三类涉及鞘氨醇单胞菌、鞘氨醇单胞菌等，有助于降解污染物，但也可能引起上皮损伤和慢性炎症。 RNA-seq 强调了 IL17、Ras、MAPK 和 Notch 通路，这些通路与癌发生和免疫系统受损相关。肺部微生物群在致癌过程中发挥着重要作用。 FLC 和 IAP 受试者受到脆弱的肺上皮、脆弱的宿主微生物平衡以及失调的免疫监视和反应的影响。我们的研究结果为研究环境致癌物、人群遗传背景和多样化肺部微生物组之间的三重相互作用提供了有用的信息。
Inherited susceptibility and environmental carcinogens are crucial players in lung cancer etiology. The lung microbiome is getting rising attention in carcinogenesis. The present work sought to investigate the microbiome in lung cancer patients affected by familial lung cancer (FLC) and indoor air pollution (IAP); and further, to compare host gene expression patterns with their microbiome for potential links. Tissue sample pairs (cancer and adjacent nonmalignant tissue) were used for 16S rRNA (microbiome) and RNA-seq (host gene expression). Subgroup microbiome diversities and their matched gene expression patterns were analyzed. Significantly enriched taxa were screened out, based on different clinicopathologic characteristics. Our FLC microbiome seemed to be smaller, low-diversity, and inactive to change; we noted microbiome differences in gender, age, blood type, anatomy site, histology type, TNM stage as well as IAP and smoking conditions. We also found smoking and IAP dramatically decreased specific-OTU biodiversity, especially in normal lung tissue. Intriguingly, enriched microbes were in three categories: opportunistic pathogens, probiotics, and pollutant-detoxication microbes; this third category involved Sphingomonas, Sphingopyxis, etc. which help degrade pollutants, but may also cause epithelial damage and chronic inflammation. RNA-seq highlighted IL17, Ras, MAPK, and Notch pathways, which are associated with carcinogenesis and compromised immune system. The lung microbiome can play vital roles in carcinogenesis. FLC and IAP subjects were affected by fragile lung epithelium, vulnerable host-microbes equilibrium, and dysregulated immune surveillance and response. Our findings provided useful information to study the triple interplay among environmental carcinogens, population genetic background, and diversified lung microbiome.