肺腺癌 (LUAD) 患者的肠道菌群仍未被探索。本研究旨在表征 LUAD 患者的肠道菌群特征，并评估肠道真菌作为非侵入性生物标志物用于早期诊断的潜力。总共前瞻性收集了来自北京、苏州和海南的 299 份粪便样本。使用内部转录间隔区 2 测序，我们对肠道真菌组进行了分析。在由 105 名 LUAD 患者和来自北京的 61 名健康对照 (HC) 组成的发现队列中，对五种监督机器学习算法进行了真菌特征训练，以构建 LUAD 的优化预测模型。来自北京、苏州和海南的验证队列分别由 44、17 和 15 名 LUAD 患者以及 26、19 和 12 名 HC 组成，用于评估疗效。 LUAD 患者的真菌多样性和丰富度有所增加。在门水平上，LUAD患者子囊菌门丰度下降，而担子菌门丰度增加。念珠菌属和酵母菌属是优势菌属，LUAD 患者中念珠菌属减少，酵母菌属、曲霉属和伞霉菌属增加。选择了 19 个可操作的分类单元标记，使用随机森林模型在预测 LUAD 方面取得了优异的性能（曲线下面积 (AUC) = 0.9350），其结果优于其他四种算法。北京、苏州和海南验证队列的 AUC 分别为 0.9538、0.9628 和 0.8833。首次显示 LUAD 患者的肠道真菌谱代表了早期诊断的潜在非侵入性生物标志物。 © 2023。作者。

The gut mycobiome of patients with lung adenocarcinoma (LUAD) remains unexplored. This study aimed to characterize the gut mycobiome in patients with LUAD and evaluate the potential of gut fungi as non-invasive biomarkers for early diagnosis.In total, 299 fecal samples from Beijing, Suzhou, and Hainan were collected prospectively. Using internal transcribed spacer 2 sequencing, we profiled the gut mycobiome. Five supervised machine learning algorithms were trained on fungal signatures to build an optimized prediction model for LUAD in a discovery cohort comprising 105 patients with LUAD and 61 healthy controls (HCs) from Beijing. Validation cohorts from Beijing, Suzhou, and Hainan comprising 44, 17, and 15 patients with LUAD and 26, 19, and 12 HCs, respectively, were used to evaluate efficacy.Fungal biodiversity and richness increased in patients with LUAD. At the phylum level, the abundance of Ascomycota decreased, while that of Basidiomycota increased in patients with LUAD. Candida and Saccharomyces were the dominant genera, with a reduction in Candida and an increase in Saccharomyces, Aspergillus, and Apiotrichum in patients with LUAD. Nineteen operational taxonomic unit markers were selected, and excellent performance in predicting LUAD was achieved (area under the curve (AUC) = 0.9350) using a random forest model with outcomes superior to those of four other algorithms. The AUCs of the Beijing, Suzhou, and Hainan validation cohorts were 0.9538, 0.9628, and 0.8833, respectively.For the first time, the gut fungal profiles of patients with LUAD were shown to represent potential non-invasive biomarkers for early-stage diagnosis.© 2023. The Author(s).