Could gut microbiota serve as prognostic biomarker associated with colorectal cancer patients' survival? A pilot study on relevant mechanism

// Zhiliang Wei 1 , Shougen Cao 1 , Shanglong Liu 1 , Zengwu Yao 2 , Teng Sun 3 , Yi Li 1 , Jiante Li 1 , Dongfeng Zhang 4 , Yanbing Zhou 1 1 Department of General Surgery, Affiliated Hospital of Qingdao University, Qingdao, China 2 Department of General Surgery, Yantai Yuhuangding Hospital, Yantai, China 3 Department of General Surgery, Qingdao Municipal Hospital Group, Qingdao, China 4 Department of Epidemiology and Health Statistics, Qingdao University Medical College, Qingdao, China Correspondence to: Yanbing Zhou, email: zhouyanbing999@aliyun.com Keywords: colorectal cancer, inflammation, intestinal microbiology, prognostic biomarker, prognosis Received: February 24, 2016      Accepted: June 02, 2016      Published: June 15, 2016 ABSTRACT Evidences have shown that dysbiosis could promote the progression of colorectal cancer (CRC). However, the association of dysbiosis and prognosis of CRC is barely investigated. Therefore, we used 16S rRNA gene sequencing approach to determine differences in microbiota among tumor tissues of different prognosis and found that Fusobacterium nucleatum and Bacteroides fragilis were more abundant in worse prognosis groups, while Faecalibacterium prausnitzii displayed higher abundance in survival group. To further explore the prognostic value of the found bacteria, Kaplan–Meier and Cox proportional regression analyses were used and the results exhibited that high abundance of F. nucleatum and B. fragilis were independent indicators of poor patient’s survival. Besides, the expression of major inflammatory mediator were analyzed using PCR and western blot methods, and it turned out that high abundance of F. nucleatum was associated with increased expression of TNF-α, β-catenin and NF-κB, while COX-2, MMP-9 and NF-κB were positively related with high B. fragilis level, and high level of F. prausnitzii showed lower expression of β-catenin, MMP-9 and NF-κB. Moreover, immunohistochemical analysis indicated that KRAS and BRAF expression were prominent in F. nucleatum and B. fragilis high abundance group, while MLH1 showed lower expression. In conclusion, F. nucleatum , B. fragilis and F. prausnitzii can be identified as useful prognostic biomarkers for CRC, and dysbiosis might worsen the patients’ prognosis by up-regulating gut inflammation level.