Tissue-resident microbiota impacts colorectal cancer progression and prognosis
Zhun Shi, Huahui Ren, Cong Lin, Fuqiang Li, Meizhen Wu, Fangming Yang, Tian Luo, Luís Nunes, Anders Isaksson, Klara Hammarström, Ting Zhu, Shida Zhu, Yiyi Zhong, Ingrid Ljuslinder, Mathias Uhlén, Richard Palmqvist, Bengt Glimelius, Kui Wu, Tobias Sjöblom, Huanzi Zhong
Abstract
To deepen the understanding of tissue-resident microbiota in colorectal cancer (CRC), we analyzed whole-genome and transcriptome data from 937 patients. We identified 249 genera and 361 species commonly present in both tumors and adjacent normal tissues (NATs). Distinct microbial signatures were associated with anatomical location, tumor stages, hypermutation status, mutations in CRC driver and DNA damage repair genes, as well as consensus molecular subtypes (CMSs). Notably, the presence of the pks island and elevated abundance of Enterobacteriaceae were linked to poor prognosis specifically in CMS2 tumors. Finally, microbial risk scores derived from taxa present in tumor or NATs predicted patient prognosis independently of established clinico-molecular factors. Prognostic taxa were strongly associated with tumor transcriptomic pathways related to hypoxia, immune response, and metabolic status. These findings revealed the heterogeneity of tissue-resident microbiota and their critical role in CRC progression, highlighting potential avenues for targeted intervention. Here, the authors show that colorectal tumors harbor diverse tissue-resident microbes whose compositions vary by tumor location and host genomics, and identify specific microbial signatures that predict patient prognosis beyond established clinical factors.