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Abstract
Purpose: There are ongoing investigations to find promising biomarkers for predicting a complete response (CR) after concurrent chemoradiation (CCRT) in rectal cancer. We aimed to find the predictive value in the gut microbiome in terms of response after preoperative CCRT.

Methods and materials: We collected a total of 45 fecal samples from patients with rectal cancer before CCRT. Tumor response after CCRT was assessed according to the American Joint Committee on Cancer tumor regression grading system. Analysis of linear discriminant analysis effect size and MetaCyc pathway abundance predictions were performed to compare composition and metabolic function of microbiome between patients with and without CR. We also established a Bayesian network model to identify microbial networks and species to be related with CCRT response.

Results: Seven patients (15.6%) demonstrated pathologically CR, and 38 patients (84.4%) showed non-CR after preoperative CCRT. Between CR and non-CR patients, there was a significant difference in terms of β-diversity (P = .028), but no difference in α-diversity was found. Bacteroidales (Bacteroidaceae, Rikenellaceae, Bacteroides) were relatively more abundant in patients with non-CR than those with CR. Pathways related to anabolic function predominated in CR patients. According to Bayesian network analysis, Duodenibacillus massiliensis was linked with the improved CR rate.

Conclusions: From the fecal microbiome using samples obtained before preoperative CCRT, differences in microbial community composition and functions were observed between patients with and without CR in rectal cancer. However, the finding that a specific taxon may be linked with the improved therapeutic response should be verified in a prospective setting.

--> LEfSe 분석으로 CR을 보인군과 그렇지 않은 군을 비교한 그림. (A) CR을 보인 군과 그렇지 않은 군 사이의 계통적 관게를 표시한 cladogram. (B) LEfSe 분석의 결과를 쉽게 표현한 상관관계 네트워크. (C) 두 군과 차이를 보이는 균주들의 Log10 LDA 값을 바 그래프로 표현함.

--> MetaCyc pathway를 계산했을 때 CR을 보인 군이 anabolic function을 가진 pathway abundance가 많이 활성화됨을 보이는 heat map.

Affiliations

Bum-Sup Jang  1 , Ji Hyun Chang  2 , Eui Kyu Chie  3 , Kyubo Kim  4 , Ji Won Park  5 , Min Jung Kim  5 , Eun-Ji Song  6 , Young-Do Nam  6 , Seung Wan Kang  7 , Seung-Yong Jeong  5 , Hak Jae Kim  8
1 Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Korea.
2 Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea.
3 Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea; Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.
4 Department of Radiation Oncology, Ewha Womans University College of Medicine, Seoul, Korea.
5 Department of Surgery, Seoul National University Hospital, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
6 Department of Food Biotechnology, Korea University of Science and Technology, Daejeon, Korea; Research Group of Healthcare, Korea Food Research Institute, Wanju, Korea.
7 Department of Nursing, Seoul National University College of Nursing, Seoul, Korea.
8 Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea; Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. Electronic address: khjae@snu.ac.kr.