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

Lejia Sun; Jiangming Qu; Xindi Ke; Yue Zhang; Hengyi Xu; Ning Lv; Jingze Leng; Yanbin Zhang; Ai Guan; Yifei Feng; Yueming Sun

doi:10.3389/fmicb.2023.1229888

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

Front Microbiol. 2023 Oct 12:14:1229888. doi: 10.3389/fmicb.2023.1229888. eCollection 2023.

Authors

Lejia Sun^{1

2

3}, Jiangming Qu⁴, Xindi Ke⁴, Yue Zhang^{1

2

3}, Hengyi Xu⁴, Ning Lv⁴, Jingze Leng⁵, Yanbin Zhang⁶, Ai Guan⁴, Yifei Feng^{1

2

3}, Yueming Sun^{1

2

3}

Affiliations

¹ Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
² The First School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
³ Colorectal Institute of Nanjing Medical University, Nanjing, China.
⁴ Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
⁵ School of Medicine, Tsinghua University, Beijing, China.
⁶ Department of Spine Surgery, Beijing Jishuitan Hospital, Beijing, China.

Abstract

Background: Previous 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.

Methods: We 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.

Results: Microbial 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).

Conclusion: Our 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.

Keywords: biomarker; cancer-associated fibroblasts; intratumoral microbiota; locally advanced rectal cancer; neoadjuvant chemoradiotherapy.

Grants and funding

This research was sponsored by China Postdoctoral Science Foundation (Grant Nos. 2023T160328 and 2023M731765), the National Natural Science Foundation of China (Grant No. 82300754), and the University Science Research Project of Jiangsu Province (Natural Science) (Grant No. 23KJB320002).