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Abstract：
Colorectal cancer (CRC) is the leading cancer worldwide. Microbial agents have been considered to contribute to the pathogenesis of different disease. But the underlying relevance between CRC and microbiota remain unclear.
We dissected the fecal microbiome structure and genomic and transcriptomic profiles of matched tumor and normal mucosa tissues from 41 CRC patients. Of which, the relationship between CRC-associated bacterial taxa and their significantly correlated somatic mutated gene was investigated by exome sequencing technology. Differentially expressed functional genes in CRC were clustered according to their correlation with differentially abundant species, following by annotation with DAVID. The composition of immune and stromal cell types was identified by XCELL.
We identified a set of 22 microbial gut species associated with CRC and estimate the relative abundance of KEGG ontology categories. Next, the interactions between CRC-related gut microbes and clinical phenotypes were evaluated. 4 significantly mutated gene: TP53, APC, KRAS, SMAD4 were pointed out and the associations with cancer related microbes were identified. Among them, Fusobacterium nucleatum positively corelated with different host metabolic pathways. Finally, we revealed that Fusobacterium nucleatum modified the tumor immune environment by TNFSF9 gene expression.
Collectively, our multi-omics data could help identify novel biomarkers to inform clinical decision-making in the detection and diagnosis of CRC.
We dissected the fecal microbiome structure and genomic and transcriptomic profiles of matched tumor and normal mucosa tissues from 41 CRC patients. Of which, the relationship between CRC-associated bacterial taxa and their significantly correlated somatic mutated gene was investigated by exome sequencing technology. Differentially expressed functional genes in CRC were clustered according to their correlation with differentially abundant species, following by annotation with DAVID. The composition of immune and stromal cell types was identified by XCELL.
We identified a set of 22 microbial gut species associated with CRC and estimate the relative abundance of KEGG ontology categories. Next, the interactions between CRC-related gut microbes and clinical phenotypes were evaluated. 4 significantly mutated gene: TP53, APC, KRAS, SMAD4 were pointed out and the associations with cancer related microbes were identified. Among them, Fusobacterium nucleatum positively corelated with different host metabolic pathways. Finally, we revealed that Fusobacterium nucleatum modified the tumor immune environment by TNFSF9 gene expression.
Collectively, our multi-omics data could help identify novel biomarkers to inform clinical decision-making in the detection and diagnosis of CRC.
摘要：
背景：结直肠癌（CRC）是全球主要癌症。微生物剂已被认为有助于不同疾病的发病机理。但CRC与微生物群之间的潜在相关性仍不清楚。
方法：我们解剖了41例CRC患者的匹配肿瘤和正常粘膜组织的粪便微生物组结构以及基因组和转录组概况。其中，通过外显子组测序技术研究了CRC相关细菌类群与其显著相关的体细胞突变基因之间的关系。CRC中差异表达的功能基因根据其与差异丰富的物种的相关性进行聚类。下面是带有DAVID的注释。免疫和基质细胞类型的组成由XCELL鉴定。
结果：我们确定了一组与CRC相关的22种微生物肠道物种，并估计了KEGG本体类别的相对丰度。接下来,评估了CRC相关肠道微生物与临床表型之间的相互作用.4个显著突变的基因：TP53，APC，KRAS,指出了SMAD4，并鉴定了与癌症相关微生物的关联。其中,核梭杆菌与不同宿主代谢途径呈正相关。最后,我们发现核梭杆菌通过TNFSF9基因的表达改变了肿瘤的免疫环境。
结论：总的来说，我们的多组学数据可以帮助识别新的生物标志物,为CRC检测和诊断的临床决策提供信息.
方法：我们解剖了41例CRC患者的匹配肿瘤和正常粘膜组织的粪便微生物组结构以及基因组和转录组概况。其中，通过外显子组测序技术研究了CRC相关细菌类群与其显著相关的体细胞突变基因之间的关系。CRC中差异表达的功能基因根据其与差异丰富的物种的相关性进行聚类。下面是带有DAVID的注释。免疫和基质细胞类型的组成由XCELL鉴定。
结果：我们确定了一组与CRC相关的22种微生物肠道物种，并估计了KEGG本体类别的相对丰度。接下来,评估了CRC相关肠道微生物与临床表型之间的相互作用.4个显著突变的基因：TP53，APC，KRAS,指出了SMAD4，并鉴定了与癌症相关微生物的关联。其中,核梭杆菌与不同宿主代谢途径呈正相关。最后,我们发现核梭杆菌通过TNFSF9基因的表达改变了肿瘤的免疫环境。
结论：总的来说，我们的多组学数据可以帮助识别新的生物标志物,为CRC检测和诊断的临床决策提供信息.
