Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, China.
School of Medicine, Xiamen University, Xiamen, Fujian, China.
Theranostics. 2021 Mar 5;11(10):4945-4956. doi: 10.7150/thno.55209. eCollection 2021.
Bacterial infection is associated with gastric carcinogenesis. However, the relationship between nonbacterial components and gastric cancer (GC) has not been fully explored. We aimed to characterize the fungal microbiome in GC. We performed ITS rDNA gene analysis in cancer lesions and adjacent noncancerous tissues of 45 GC cases from Shenyang, China. Obtaining the OTUs and combining effective grouping, we carried out species identifications, alpha and beta diversity analyses, and FUNGuild functional annotation. Moreover, differences were compared and tested between groups to better investigate the composition and ecology of fungi associated with GC and find fungal indicators. We observed significant gastric fungal imbalance in GC. Principal component analysis revealed separate clusters for the GC and control groups, and Venn diagram analysis indicated that the GC group showed a lower OTU abundance than the control. At the genus level, the abundances of 15 fungal biomarkers distinguished the GC group from the control, of which ( = 0.000246) and ( = 0.00341) were enriched in GC, while ( = 0.002324) and ( = 0.009158) were decreased. Combining the results of Welch's t test and Wilcoxon rank sum test, () was significantly elevated in GC. The species richness Krona pie chart further revealed that occupied 22% and classified GC from the control with an area under the receiver operating curve (AUC) of 0.743. Random forest analysis also confirmed that could serve as a biomarker with a certain degree of accuracy. Moreover, compared with that of the control, the alpha diversity index was significantly reduced in the GC group. The Jaccard distance index and the Bray abundance index of the PCoA clarified separate clusters between the GC and control groups at the species level ( = 0.00051). Adonis (PERMANOVA) analysis and ANOVA showed that there were significant differences in fungal structure among groups ( = 0.001). Finally, FUNGuild functional classification predicted that saprotrophs were the most abundant taxa in the GC group. This study revealed GC-associated mycobiome imbalance characterized by an altered fungal composition and ecology and demonstrated that can be a fungal biomarker for GC. With the significant increase of in GC, the abundance of were increased, while , and were obviously decreased. In addition, may mediate GC by reducing the diversity and richness of fungi in the stomach, contributing to the pathogenesis of GC.
细菌感染与胃癌的发生有关。然而，非细菌性成分与胃癌（GC）的关系尚未得到充分探索。我们旨在描述 GC 中的真菌微生物组。我们对来自中国沈阳的 45 例 GC 病例的癌灶和相邻非癌组织进行了 ITS rDNA 基因分析。获得 OTUs 并结合有效分组，我们进行了物种鉴定、alpha 和 beta 多样性分析以及 FUNGuild 功能注释。此外，还比较和测试了组间差异，以更好地研究与 GC 相关的真菌组成和生态，并找到真菌指标。我们观察到 GC 中存在明显的胃真菌失衡。主成分分析显示 GC 组和对照组有单独的聚类，Venn 图分析表明 GC 组的 OTU 丰度低于对照组。在属水平上，区分 GC 组和对照组的 15 种真菌生物标志物中，（=0.000246）和（=0.00341）在 GC 中富集，而（=0.002324）和（=0.009158）减少。结合 Welch's t 检验和 Wilcoxon 秩和检验的结果，（）在 GC 中显著升高。Krona 饼图的物种丰富度进一步表明，在 GC 中占 22%，并以 0.743 的接收者操作曲线（AUC）将 GC 与对照组区分开来。随机森林分析也证实，（）可以作为一种具有一定准确性的生物标志物。此外，与对照组相比，GC 组的 alpha 多样性指数显著降低。GC 和对照组之间在物种水平上的 Jaccard 距离指数和 Bray 丰度指数的 PCoA 进一步阐明了分开的聚类（=0.00051）。Adonis（PERMANOVA）分析和 ANOVA 表明，组间的真菌结构存在显著差异（=0.001）。最后，FUNGuild 功能分类预测，腐生菌是 GC 组中最丰富的类群。本研究揭示了 GC 相关的 mycobiome 失衡，其特征是真菌组成和生态发生改变，并表明（）可以作为 GC 的真菌生物标志物。随着 GC 中（）的显著增加，（）的丰度增加，而（）、（）和（）明显减少。此外，（）可能通过减少胃中真菌的多样性和丰富度来介导 GC，从而促进 GC 的发病机制。
