University of Chile and TMDU Joint Degree Doctoral Program in Medical Sciences with Mention of a Medical Specialty, Tokyo Medical and Dental University, Bunkyo-Ku, Tokyo, Japan
Yuriko Matsumiya , Mitsukuni Suenaga , Toshiaki Ishikawa , Marie Hanaoka , Noriko Iwata , Taiki Masuda , Shinichi Yamauchi , Masanori Tokunaga , Yusuke Kinugasa
Background: Bacteroides fragilis (B. fragilis) is an obligate anaerobe and generally acts as anti-inflammatory manner on the intestinal tract. Enterotoxigenic Bacteroides fragilis (ETBF), a subtype of B. fragilis, produces Bacteroides fragilis toxin (BFT) leading to either asymptomatic chronic colonic inflammation or colonic tumor formation. However, the impact of B. fragilis and ETBF on colorectal cancer (CRC) prognoses still remains unclear. We tested whether the presence of B. fragilis and ETBF affect clinical outcome in CRC patients who underwent curative surgery. Methods: We obtained 197 pairs of matched FFPE samples from colorectal cancerous and adjusted non-cancerous tissues of patients with stage II and III CRC who underwent curative resection between 2014 and 2016. Quantitative analyses of B. fragilis and ETBF in the colon tissues were performed using quantitative PCR with primers, 16S rRNA for B. fragilis and bft DNA, respectively. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression. Results: Among 197 patients, 16S rRNA for B. fragilis DNA and bft DNA were detected in 120 patients (60.9%) and 12 patients (6.1%), respectively. B. fragilis-positive patients had better RFS (5-y RFS rate: 81.4% vs. 73.4%, HR0.59, 95% CI: 0.31-1.12, p =0.10) and OS (5-y OS rate: 88.9% vs 78.3%, HR0.53, 95% CI: 0.26-1.11, p =0.091) compared with B. fragilis-negative patients though statistically not significant. In multivariable analysis for RFS, B. fragilis-positive remained as an independent prognostic factor (HR0.53, 95% CI: 0.28-0.99, p =0.049) along with tumor depth T4 and Stage III, while there was no significance in OS. No significant differences were observed between ETBF and nontoxigenic B. fragilis in patients' characteristics and clinical outcomes. Conclusions: Our findings suggest that the presence of B. fragilis may predict outcome especially RFS in patients with curatively resected stage II and III CRC. Further research are warranted to explore whether B. fragilis status could be involved in a novel prediction model for outcome in early-stage CRC and develop probiotics treatments to prevent recurrence.
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