80MO - Gut microbiome analysis for predicting neoadjuvant chemoradiotherapy response in locally advanced rectal cancer patients

Background

The gut microbiome has been reported to be involved in antitumour immunotherapy and chemotherapy responses; however, evidence-based research on the role of the gut microbiome in neoadjuvant chemoradiotherapy (nCRT) responses of locally advanced rectal cancer (LARC) patients is scarce. This research aims to evaluate the feasibility of the gut microbiome in predicting nCRT responses in LARC patients.

Methods

We collected 167 faecal samples from 84 LARC patients before and after nCRT in our institution and 31 faecal samples from healthy individuals for 16S ribosomal RNA sequencing. We used the AJCC tumour regression grade (TRG) system to evaluate the nCRT responses and accordingly divided patients into two groups. Patients with TRG scores of 0-1 were grouped as responders (R group), and those with TRG scores of 2-3 were grouped as non-responders (NR group). After characterizing the gut microbiome and identifying biomarker bacteria related to nCRT responses, we constructed a random forest classifier for nCRT response prediction of a training set of 37 baseline samples and validated the classifier with the remaining 47 baseline samples.

Results

Taxonomic differences in relation to nCRT responses were noticed in baseline faecal samples, including overrepresentation of butyrate-producing bacteria (Dorea and Anaerostipes) in R, and overrepresentation of Coriobacteriaceae and Fusobacterium in NR. During nCRT, a decline in bacterial richness related to therapeutic responses was observed. Furthermore, microbiome alterations imposed by nCRT were represented by a decrease in LARC-related pathogens and an increase in Lactobacillus and Streptococcus, and the increase of Streptococcus was exclusively shown in R subgroup. Ten variables were selected for the classifier, including Dorea, Anaerostipes and Streptococcus, and the area under the curve reached 93.57% (95% CI: 85.76%∼100.00%) in the training set and 73.53% (95% CI: 58.96%∼88.11%) in the validation set.

Conclusions

The gut microbiome plays a role in nCRT responses and provides potential biomarkers to predict nCRT responses. Further validation in a larger sample size is needed.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Fudan University Shanghai Cancer Center.

Funding

the National Natural Science Foundation of China.

Disclosure

All authors have declared no conflicts of interest.