Department of Thoracic Surgery I, the Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, China.
The International Cooperation Key Laboratory of Regional Tumor in High Altitude Area, the Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, China.
Front Immunol. 2022 Apr 11;13:827953. doi: 10.3389/fimmu.2022.827953. eCollection 2022.
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.
遗传易感性和环境致癌物是肺癌发病机制中的关键因素。肺部微生物组在致癌作用中受到越来越多的关注。本研究旨在探讨受家族性肺癌（FLC）和室内空气污染（IAP）影响的肺癌患者的微生物组，并进一步比较宿主基因表达模式与其微生物组之间的潜在联系。
使用 16S rRNA（微生物组）和 RNA-seq（宿主基因表达）对组织样本对（癌症和相邻非恶性组织）进行分析。分析了亚组微生物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著富集的分类群。
我们的 FLC 微生物组似乎较小、多样性低且不易变化；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 和吸烟状况方面存在差异。我们还发现吸烟和 IAP 显著降低了特定 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：机会性病原体、益生菌和污染物解毒微生物；这第三类包括有助于降解污染物的 Sphingomonas、Sphingopyxis 等，但也可能导致上皮损伤和慢性炎症。RNA-seq 强调了与致癌作用和受损免疫系统相关的 IL17、Ras、MAPK 和 Notch 途径。
肺部微生物组在致癌作用中可以发挥重要作用。FLC 和 IAP 患者受脆弱的肺上皮、易受宿主-微生物平衡影响以及失调的免疫监视和反应的影响。我们的发现为研究环境致癌物、人群遗传背景和多样化的肺部微生物组之间的三重相互作用提供了有用的信息。
