Tumor-Associated Microbiota in Proximal and Distal Colorectal Cancer and Their Relationships With Clinical Outcomes.

Min Jin,Jingjing Wu,Qilin Fan,Li Liu,Tao Zhang,Jun Fan,Chen Chen,Shuji Ogino,Xiu Nie,Hongli Liu,Kailin Cai,Fumei Shang

doi:10.3389/fmicb.2021.727937

Abstract

The proximal and distal subsites of colorectal cancer (CRC) have distinct differences in their embryonic origin, epidemiology, and prognosis. Therefore, they are not considered as the same disease. However, the possible difference in microbial characterization of the two subsites of CRC is still unclear. In this study, we explored tumor microbiota diversity and composition difference in patients with proximal (N = 187) and distal CRCs (N = 142). This was carried out on cancer tissues and adjacent tissues using bacterial 16S rRNA sequencing. The Kaplan–Meier method was used to analyze the correlation between differential flora and overall survival rate of the patients. It was found that there were significant differences in tumor microbial characteristics between the proximal and distal CRC tissues. The microbiota communities were distinctly richer in the proximal colon tumor tissues than in the distal CRC tissues. Microbial diversity and structure were relatively constant in the paracancerous normal tissues of the proximal and distal colorectum. Generally, microbial communities of CRC tumor tissues were composed of Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. Alpha diversity in the proximal and distal CRC tumor tissues was closely related to specific microflora. The abundance of Fusobacteria was associated with age of patient, tumor diameter, and tumor microsatellite instability (MSI) status of the patients. Moreover, Fusobacteria enrichment was associated with poor prognosis especially in patients with proximal colon cancers, but not in patients with distal CRC. In conclusion, proximal and distal subsites of the CRC present distinct microbiota diversity and community structures. The differences indicate that there are different risk factors across anatomical subsites of CRC, which may provide a new strategy for precise prevention and treatment of CRC in the future.

Highlights

Despite improvements in screening, prevention, and treatment strategies over the past decade, colorectal cancer (CRC) is the third leading malignant cancer and the fourth cause of cancerrelated deaths
BRAF mutation, microsatellite instability (MSI), the CpG island methylator phenotype (CIMP)high, or the consensus molecular subtype (CMS) CMS1 is more likely to occur in proximal CRC (Missiaglia et al, 2014; Guinney et al, 2015; Lee et al, 2017), while chromosome instability, TP53 or APC mutation, or CMS2 is more likely to occur in distal CRC (Missiaglia et al, 2014; Guinney et al, 2015; Loree et al, 2018)
Our study indicates that the abundance of Fusobacteria in CRC tumor tissues was closely related to tumor diameter, which was consistent with the report by Yamaoka et al (2018)

Summary

Introduction

Prevention, and treatment strategies over the past decade, colorectal cancer (CRC) is the third leading malignant cancer and the fourth cause of cancerrelated deaths. It is estimated that 1,849,518 new cases of CRC and 880,792 CRC-related deaths occur per year (Bray et al, 2018) This is despite notable improvements in the disease screening, prevention, and treatment strategies over the past decade. Proximal CRC commonly has a poorer prognosis than distal CRC (Petrelli et al, 2017; Cannon and Buechler, 2019). These differences between anatomical segments reflect a complex interaction between different environmental exposures of colorectal epithelial cells to carcinogenic or protective factors and the different inherent biological features affecting the risk of anatomical subsite carcinogenesis

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