Interaction between intratumoral microbiota and tumor mediates the response of neoadjuvant therapy for rectal cancer

Frontiers in Microbiology

Microbiology

Xindi Ke¹  Jiangming Qu¹  Ning Lv¹  Ai Guan¹  Hengyi Xu¹  Yifei Feng²  Lejia Sun²  Yue Zhang²  Yueming Sun²  Yanbin Zhang³  Jingze Leng⁴ 

[1] Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China;Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China;The First School of Clinical Medicine, Nanjing Medical University, Nanjing, China;Colorectal Institute of Nanjing Medical University, Nanjing, China;Department of Spine Surgery, Beijing Jishuitan Hospital, Beijing, China;School of Medicine, Tsinghua University, Beijing, China;

关键词: locally advanced rectal cancer;    neoadjuvant chemoradiotherapy;    intratumoral microbiota;    cancer-associated fibroblasts;    biomarker;   

DOI  :  10.3389/fmicb.2023.1229888

 received in 2023-05-27, accepted in 2023-09-29,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundPrevious observations have demonstrated that the response to neoadjuvant chemoradiotherapy (nCRT) is highly variable in patients with locally advanced rectal cancer (LARC). Recent studies focusing on the intratumoral microbiota of colorectal cancer have revealed its role in oncogenesis and tumor progression. However, limited research has focused on the influence of intratumoral microbiota on the nCRT of LARC.MethodsWe explored the microbial profiles in the tumor microenvironment of LARC using RNA-seq data from a published European cohort. Microbial signatures were characterized in pathological complete response (pCR) and non-pCR groups. Multi-omics analysis was performed between intratumor microbiomes and transcriptomes.ResultsMicrobial α and β diversity were significantly different in pCR and non-pCR groups. Twelve differential microbes were discovered between the pCR and non-pCR groups, six of which were related to subclusters of cancer-associated fibroblasts (CAFs) associated with extracellular matrix formation. A microbial risk score based on the relative abundance of seven differential microbes had predictive value for the nCRT response (AUC = 0.820, p < 0.001).ConclusionOur study presents intratumoral microbes as potential independent predictive markers for the response of nCRT to LARC and demonstrates the underlying mechanism by which the interaction between intratumoral microbes and CAFs mediates the response to nCRT.

【 授权许可】

Unknown   
Copyright © 2023 Sun, Qu, Ke, Zhang, Xu, Lv, Leng, Zhang, Guan, Feng and Sun.