Changes in tumor microbiome and underlying value according to response to neoadjuvan chemotherapy for in patients with gastric cancer

Abstract

Objective: To investigate the relationship between efficacy of neoadjuvant chemotherapy (NACT) for gastric cancer and gastric microecology. Methods: This was a retrospective observational study using fresh frozen operative specimens. The specimens had been stored in the tumor sample bank of the Department of Gastrointestinal Surgery of the Affiliated Hospital of Qingdao University from January 2017 to January 2023 after having been collected from 31 patients with pathologically diagnosed gastric cancer who had no metastases and had received only neoadjuvant chemotherapy preoperatively. The study patients had all successfully undergone radical gastric cancer surgery. Patients with metastases or other primary tumor foci and/or had received other therapies within 1 month prior to surgery, including immunotherapy, targeted therapies and probiotics, were excluded. The tumors were graded and grouped in accordance with the 8th edition of the American Joint Committee on Cancer staging system and the Tumor Regression Grading System (TRG) of the College of American Pathologists. Those with TRG Grades 0-1, ypT0-1 and ypN0 were classified as responsive (Group R, 12 cases), whereas those with TRG Grades 2-3 and ypT2-4 or ypN+ were classified as non-responsive (Group NR, 19 cases). The fresh frozen samples were processed and analyzed using 16S rRNA sequencing. Alpha and beta diversity analyses were performed using the Q2-diversity plug-in for QIIME2 and STAMP was used to determine the default parameters and differentially enriched bacterial taxa in the two groups. High-dimensional class comparisons were performed by effect size linear discriminant analysis, and potential functional distributions of microbiomes were predicted using PICRUST2 (v2.3.0-b) software. Results: Groups R and NR did not differ significantly in sex, age, body mass index, smoking history, tumor location, cTNM stage before NACT, and neoadjuvant chemotherapy (all P>0.05), whereas tumor size and ypTNM stage after NACT differed significantly between the two groups (both P=0.001). Alpha and beta diversity analysis of the gastric microbiota did not reveal a statistically significant difference in alpha diversity between the two groups (P>0.05), whereas there was a statistically significant difference in beta diversity between the two groups (P=0.004). Four family-level bacterial taxa, namely Coriobacteriaceae, Ruminococcaceae, Veillonellaceae, and Lachnospiraceae, were enriched in the R group, whereas four bacterial taxa dominated by phylum Proteobacteria were enriched in the NR group. Metabolic pathways of various amino acids, including citric acid cycle and alanine, were found to be potentially predictive. Conclusions: There are significant differences in the abundance and composition of gastric microecology in gastric cancer patients with different responses to NACT.