Microbiomic and immunogenic biomarkers of adjuvant chemotherapy efficacy in stage III colorectal cancer

Abstract Background The standard treatment for stage III colorectal cancer (CRC) is surgery, followed by adjuvant chemotherapy (AC). However, the efficacy of AC is limited and approximately 30% of patients experience recurrence. Therefore, easily assessable molecular biomarkers that can predict the response to AC are needed. Here, we aimed to identify predictive biomarkers of the response to AC using tumor transcriptomic data. Methods Tumor specimens from 253 patients who underwent surgery for stage III CRC between 1997 and 2019 were analyzed using RNA sequencing. Transcriptional subtyping and analyses of gut microbiome, immune cell fractions, and T-cell receptors (TCRs) were performed to identify factors associated with recurrence-free survival (RFS) in patients treated with or without AC. Results Among 253 patients, 118 (46.6%) received AC. Twenty phyla and 799 species were identified in the microbiomes, among which Fusobacteria were identified in 247 patients (97.6%). Multivariable Cox proportional hazards regression analysis of patients who received AC showed that intratumoral Fusobacterium abundance (hazard ratio HR, 3.95; 95% confidence interval CI, 1.05 to 14.8; P = 0.042) and TCR α and δ (TRAD) diversity (HR, 0.41; 95% CI, 0.20 to 0.87; P = 0.020) were independently associated with RFS. Conclusion Fusobacterium abundance and TRAD diversity were associated with the response to AC, suggesting that these factors could serve as biomarkers for personalized treatment in stage III CRC.