A comprehensive analysis of the microbiota composition and gene expression in colorectal cancer

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RESEARCH ARTICLE

Open Access

A comprehensive analysis of the microbiota composition and gene expression in colorectal cancer Qian Zhang1,2, Huan Zhao1, Dedong Wu2, Dayong Cao3 and Wang Ma1*

Abstract Background: The dysregulation of gut microbiota is pivotal in colorectal carcinogenesis. Meanwhile, altered gut microbiome may affect the development of intestinal diseases through interaction with the host genes. However, the synergy between the altered gut microbiota composition and differential expression of specific genes in colorectal cancer (CRC) remains elusive. Thus, we integrated the data from 16S rRNA gene sequences and RNA sequences to investigate the potential relationship between genes and gut microbes in patients with CRC. Results: Compared with normal samples, the presence of Proteobacteria and Fusobacteria increased considerably in CRC samples; conversely, the abundance of Firmicutes and Spirochaetes decreased markedly. In particular, the genera Fusobacterium, Catenibacterium, and Shewanella were only detected in tumor samples. Meanwhile, a closely interaction between Butyricimonas and Clostridium was observed in the microbiome network. Furthermore, a total of 246 (differentially expressed genes) DEGs were identified between tumor and normal tissues. Both DEGs and microbiota were involved in bile secretion and steroid hormone biosynthesis pathways. Finally, genes like cytochrome P450 family 3 subfamily A member 4 (CYP3A4) and ATP binding cassette subfamily G member 2 (ABCG2) enriched in these two pathways were connected with the prognosis of CRC, and CRC patients with low expression level of CYP3A4 and ABCG2 had longer survival time. Conclusion: Identifying the complicated interaction between gut microbiota and the DEGs contributed to further understand the pathogenesis of CRC, and these findings might enable better diagnosis and treatment of CRC patients. Keywords: Colorectal cancer, Gut microflora, Gene expression, Pathways enrichment, Survival analysis

Background Colorectal cancer (CRC) is one of the primary causes of mortality and morbidity worldwide, thus representing a major public health issue [1]. Although heritable genetic mutations are closely linked to some types of CRC [2], increasing evidences indicate that diet is regarded as a notable risk factor of CRC [3, 4]. Chan et al. revealed * Correspondence: [email protected] 1 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou 450000, Henan, China Full list of author information is available at the end of the article

that excessive intake of red meat and animal fat might increase the risk of CRC [5]. It is reported that diet can modulate the composition of gut microbiota which serves a crucial role in maintaining intestinal homeostasis and is involved in the regulation of host inflammation and immune responses [6]. Different members of the intestinal microbiota can jointly regulate the host immune and metabolic systems, subsequently producing carcinogenic or a