Unravelling the prognostic and operative role of intratumoural microbiota in non-small cell lung cancer: Insights from 16S rRNA and RNA sequencing

IF 7.9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Clinical and Translational Medicine Pub Date : 2025-01-03 DOI:10.1002/ctm2.70156

Fuling Mao, Zixuan Hu, Ruifeng Shi, Hongbing Zhang, Zihe Zhang, Yongwen Li, Xuanguang Li, Penghu Gao, Jinhui Li, Minghui Liu, Hongyu Liu, Jun Chen

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Key points

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.

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揭示非小细胞肺癌肿瘤内微生物群的预后和手术作用：来自16S rRNA和RNA测序的见解。

背景：微生物群和癌症之间复杂的相互关系已经被一些研究确定。然而，尽管描述了非小细胞肺癌（NSCLC）的微生物组成，但主要致病微生物群及其潜在机制仍不清楚。方法：对30例非小细胞肺癌患者的癌旁正常组织样本进行16S rRNA V3-V4扩增子和转录组测序，收集其临床特征和预后结果。我们使用16S rRNA测序来解剖微生物组成并执行预后相关性，并结合转录组测序，我们确定了支持重要微生物群作用的潜在机制。结果：在比较不同的样本类型时，我们发现NSCLC、肺鳞状细胞癌（LUSC）和相应的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。随后筛选出与预后相关的4门5纲9目17科36属。有趣的是，一个保护性微生物群被确定包括9个与延迟疾病复发相关的属，功能分析表明这些微生物群主要发挥代谢相关功能。此外，还鉴定出一个有害微生物群（HMC），包括3个属。在这个HMC和随后的预后模型分析中，有害的肿瘤内微生物群可能与感染、炎症和免疫调节有关。至关重要的是，我们确定了一种微生物属，Peptococcus，它是一种独立的、有害的NSCLC预后因素，并可能通过肿瘤坏死因子（TNF）信号传导影响预后结果。结论：我们确定了肿瘤内微生物群与非小细胞肺癌预后之间的实质性联系。保护性微生物群主要发挥代谢功能，而有害微生物群主要参与感染、炎症和免疫调节。此外，Peptococcus可能在不良的NSCLC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。重点：已发现4门5纲9目17科36属与NSCLC预后相关。我们发现了与延迟复发相关的保护性微生物群和与较短生存期和早期复发相关的有害微生物群。我们确定了Peptococcus是NSCLC的一个独立的、有害的预后因素，可能通过TNF信号传导影响预后。

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来源期刊

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.