Mao Fuling, Hu Zixuan, Shi Ruifeng, Zhang Hongbing, Zhang Zihe, Li Yongwen, Li Xuanguang, Gao Penghu, Li Jinhui, Liu Minghui, Liu Hongyu, Chen Jun
Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China.
Clin Transl Med. 2025 Jan;15(1):e70156. doi: 10.1002/ctm2.70156.
Complex interrelationships between the microbiota and cancer have been identified by several studies. However, despite delineating microbial composition in non-small cell lung cancer (NSCLC), key pathogenic microbiota and their underlying mechanisms remain unclear.
We performed 16S rRNA V3-V4 amplicon and transcriptome sequencing on cancerous and adjacent normal tissue samples from 30 patients with NSCLC, from which clinical characteristics and prognosis outcomes were collected. We used 16S rRNA sequencing to dissect microbial composition and perform prognosis correlations, and in conjunction with transcriptome sequencing, we determined potential mechanisms underpinning significant microbiota actions.
In comparing different sample types, we identified more pronounced beta diversity disparity between NSCLC, lung squamous cell carcinoma (LUSC) and corresponding paired normal tissues. Concurrently, LUSC and lung adenocarcinoma exhibited distinct microbial composition traits at genus levels. Subsequently, four phyla, five classes, nine orders, 17 families and 36 genera were filtered out and were related to prognosis outcomes. Intriguingly, a protective microbial cluster was identified encompassing nine genera associated with delayed disease recurrence, with functional analyses suggested that these microbiota predominantly exerted metabolism-related functions. Additionally, a harmful microbial cluster (HMC) was identified, including three genera. In this HMC and subsequent prognosis model analyses, harmful intratumoural microbiota were potentially implicated in infection, inflammation and immune regulation. Crucially, we identified a microbial genus, Peptococcus, which was as an independent, detrimental NSCLC prognostic factor and potentially impacted prognosis outcomes via tumour necrosis factor (TNF) signalling.
We identified a substantial connection between intratumoural microbiota and NSCLC prognosis outcomes. Protective microbiota primarily exerted metabolic functions, whereas harmful microbiota were mainly implicated in infection, inflammation and immune modulation. Furthermore, Peptococcus may be significant in adverse NSCLC prognoses and serve as a potential biomarker for patient management and cancer screening.
Four phyla, five classes, nine orders, 17 families and 36 genera have been found associated with NSCLC prognosis. We identified a protective microbial cluster associated with delayed recurrence and a harmful microbial cluster related to shorter survival and earlier recurrence. We identified Peptococcus as an independent, detrimental prognostic factor for NSCLC, potentially impacting prognosis via TNF signalling.
多项研究已确定微生物群与癌症之间存在复杂的相互关系。然而，尽管已明确非小细胞肺癌（NSCLC）中的微生物组成，但关键的致病微生物群及其潜在机制仍不清楚。
我们对30例NSCLC患者的癌组织和癌旁正常组织样本进行了16S rRNA V3-V4扩增子和转录组测序，并收集了临床特征和预后结果。我们使用16S rRNA测序剖析微生物组成并进行预后相关性分析，并结合转录组测序，确定了微生物群显著作用的潜在机制。
在比较不同样本类型时，我们发现NSCLC、肺鳞状细胞癌（LUSC）与相应配对正常组织之间的β多样性差异更为明显。同时，LUSC和肺腺癌在属水平上表现出不同的微生物组成特征。随后，筛选出与预后结果相关的4个门、5个纲、9个目、17个科和36个属。有趣的是，我们鉴定出一个保护性微生物簇，包含9个与疾病复发延迟相关的属，功能分析表明这些微生物群主要发挥与代谢相关的功能。此外，还鉴定出一个有害微生物簇（HMC），包括3个属。在这个HMC及后续预后模型分析中，肿瘤内有害微生物群可能与感染、炎症和免疫调节有关。至关重要的是，我们鉴定出一个微生物属——消化球菌，它是NSCLC独立的不良预后因素，并可能通过肿瘤坏死因子（TNF）信号通路影响预后结果。
我们确定了肿瘤内微生物群与NSCLC预后结果之间的实质性联系。保护性微生物群主要发挥代谢功能，而有害微生物群主要与感染、炎症和免疫调节有关。此外，消化球菌可能在NSCLC不良预后中具有重要意义，并可作为患者管理和癌症筛查的潜在生物标志物。
已发现4个门、5个纲、9个目、17个科和36个属与NSCLC预后相关。我们鉴定出一个与复发延迟相关的保护性微生物簇和一个与生存期较短及复发较早相关的有害微生物簇。我们鉴定出消化球菌是NSCLC独立的不良预后因素，可能通过TNF信号通路影响预后。
