Liu Fan, Lu Xingbing, Tang Mengli, Chen Yuzuo, Zheng Xi
Health Management Center, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Cancer Manag Res. 2025 Jan 11;17:45-56. doi: 10.2147/CMAR.S499003. eCollection 2025.
OBJECTIVE: Our research has pinpointed the gut microbiome's role in the progression of various pathological types of non-small cell lung cancer (NSCLC). Nonetheless, the characteristics of the gut microbiome and its metabolites across different clinical stages of NSCLC are yet to be fully understood. The current study seeks to explore the distinctive gut flora and metabolite profiles of NSCLC patients across varying TNM stages. METHODS: The research team gathered stool samples from 52 patients diagnosed with non-small cell lung cancer (NSCLC) and 29 healthy individuals. Subsequently, they performed 16S rRNA gene amplification sequencing and untargeted gas/liquid chromatography-mass spectrometry metabolomics analysis. RESULTS: The study revealed that the alpha-diversity of the gut microbiome in NSCLC patients at different stages did not exhibit statistically significant differences. Notably, and were more abundant in healthy controls. The distribution of gut microbial species in patients with varying stages of NSCLC was uneven, with and being most prevalent in stage T2, and dominating in stage T4. Levels of were notably elevated in stages N3 and M. The genus levels of , and were higher in stage II patients. was the bacterium with increased levels in stage III NSCLC patients. Further metabolomics studies revealed significantly elevated levels of quinic acid and 3-hydroxybenzoic acid in the healthy control group. In contrast, Stage I+II non-small cell lung cancer (NSCLC) patients exhibited reduced levels of L-cystathionine. Notably, quinic acid, phthalic acid, and L-lactic acid were observed to be increased in Stage III+IV NSCLC patients. CONCLUSION: Compared to the analysis of a single microbial dataset, this study provides deeper functional insights by incorporating comprehensive metabolomic profiling. This approach demonstrates that both the gut microbiome and associated metabolites are altered in NSCLC patients across different clinical stages. Our findings may offer novel perspectives on the pathogenesis of NSCLC at various TNM stages. Further research is warranted to validate and clinically apply these potential biomarkers.
目的：我们的研究已明确肠道微生物群在各种病理类型的非小细胞肺癌（NSCLC）进展中的作用。尽管如此，NSCLC不同临床阶段肠道微生物群及其代谢产物的特征仍有待充分了解。本研究旨在探索不同TNM分期的NSCLC患者独特的肠道菌群和代谢产物谱。 方法：研究团队收集了52例诊断为非小细胞肺癌（NSCLC）的患者和29名健康个体的粪便样本。随后，他们进行了16S rRNA基因扩增测序和非靶向气相/液相色谱-质谱代谢组学分析。 结果：研究表明，不同阶段NSCLC患者肠道微生物群的α多样性无统计学显著差异。值得注意的是，[具体菌属1]和[具体菌属2]在健康对照中更为丰富。NSCLC不同阶段患者的肠道微生物种类分布不均，[具体菌属3]和[具体菌属4]在T2期最为普遍，[具体菌属5]在T4期占主导。N3期和M期[某种物质]水平显著升高。II期患者中[具体菌属6]、[具体菌属7]和[具体菌属8]的属水平较高。[具体菌属9]是III期NSCLC患者中水平升高的细菌。进一步的代谢组学研究显示，健康对照组中奎尼酸和3-羟基苯甲酸水平显著升高。相比之下，I+II期非小细胞肺癌（NSCLC）患者的L-胱硫醚水平降低。值得注意的是，III+IV期NSCLC患者中奎尼酸、邻苯二甲酸和L-乳酸增加。 结论：与单一微生物数据集分析相比，本研究通过纳入全面的代谢组学分析提供了更深入的功能见解。这种方法表明，NSCLC患者在不同临床阶段肠道微生物群和相关代谢产物均发生改变。我们的发现可能为NSCLC在不同TNM阶段的发病机制提供新的视角。有必要进一步研究以验证并临床应用这些潜在的生物标志物。
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