不吸烟肺癌中协调的微生物-炎症关联
Coordinated microbial-inflammatory associations in never-smoking lung cancer.
作者
作者单位
- Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21021, USA.
- Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21021, USA; BIOTARGET DX LLC, 4 N Martin Luther King Jr Blvd, Baltimore, MD 21021, USA. Electronic address: fjiang@som.umaryland.edu.
摘要
中文
虽然吸烟是肺癌的主要原因，但不吸烟者中发病率的增加日益引起关注，凸显了非烟草相关的致癌机制。新出现的证据表明，呼吸道微生物失调和相关炎症反应可能促进肺肿瘤发生。我们先前表明，Selenomonas、Streptococcus 和 Veillonella 的丰度升高与肺癌相关，与吸烟史无关。在这里，我们检查了不吸烟者中循环微生物和炎症特征是否与肺癌相关。通过微滴式数字 PCR 定量代表这三个属的循环细菌 DNA，并通过 ELISA 测量 56 名曾吸烟肺癌患者、56 名不吸烟肺癌患者和 78 名健康对照者血浆中的七种全身炎症细胞因子。进行了综合统计建模以评估细菌 DNA 负荷、炎症激活、吸烟史和癌症状态之间的关系。与对照组相比，肺癌患者的 Selenomonas、Streptococcus 和 Veillonella 的血浆 DNA 水平以及 IL-6、TNF-α、IL-1β、IL-8 和 IL-17A 均升高（均 p < 0.05）。吸烟和不吸烟肺癌患者之间的细菌 DNA 水平、IL-6、TNF-α 或 IL-17A 未观察到显著差异（均 > 0.05），而 IL-8（P = 0.036）和 IL-1β（P = 0.048）观察到适度但统计学显著的差异。细菌 DNA 负荷与全身炎症细胞因子激活相关，与吸烟史无关（均 p < 0.05）。吸烟无关的微生物-炎症特征与肺癌相关，并为未来评估其生物学意义和诊断管理临床效用提供了基础。
English
While smoking is the leading cause of lung cancer, the increasing incidence among never-smokers is a growing concern, highlighting non-tobacco-related mechanisms of carcinogenesis. Emerging evidence suggests that respiratory microbial dysbiosis and associated inflammatory responses may contribute to lung tumorigenesis. We previously showed that elevated abundances of Selenomonas, Streptococcus, and Veillonella are correlated with lung cancer independent of smoking history. Here, we examine whether circulating microbial and inflammatory profiles are linked to lung cancer in never-smokers. Circulating bacterial DNA representing the three genera was quantified by droplet digital PCR, and seven systemic inflammatory cytokines were measured by ELISA in plasma of 56 ever-smoker lung cancer patients, 56 never-smoker lung cancer patients, and 78 healthy controls. Integrative statistical modeling was performed to evaluate relationships among bacterial DNA burden, inflammatory activation, smoking history, and cancer status. Plasma DNA levels of Selenomonas, Streptococcus, and Veillonella, together with IL-6, TNF-α, IL-1β, IL-8, and IL-17A, were elevated in lung cancer patients compared with controls (all p < 0.05). No significant differences were observed between smoking and never-smoking lung cancer patients for bacterial DNA levels, IL-6, TNF-α, or IL-17A (all > 0.05), whereas modest but statistically significant differences were observed for IL-8 (P = 0.036) and IL-1β (P = 0.048). Bacterial DNA burden was correlated with systemic inflammatory cytokine activation independent of smoking history (all p < 0.05). A smoking-independent microbial-inflammatory signature is associated with lung cancer and provides a foundation for future studies evaluating its biological significance and clinical utility for diagnosis and management.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 5.3
- 新锐分区
- 2区