Development of a Microbiome-Based Prognostic Signature for Survival Prediction and Therapeutic Stratification in Colorectal Cancer

Shiyi Xu; Hong Ye; Xuejie Gao

doi:10.18282/po4736

Shiyi Xu College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics , Fujian Medical University
Hong Ye ^* Fujian Children’s Hospital(Fujian Branch of Shanghai Children’s Medical Center); College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University
Xuejie Gao Fujian Children’s Hospital(Fujian Branch of Shanghai Children’s Medical Center); College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University

Article ID: 4736

DOI: https://doi.org/10.18282/po4736

Keywords: CRC，microbiota，prognosis，drug sensitivity

Abstract

The intratumoral bacteria effect have been highlighted recently. Inthisstudy, we developed a microbiome-based signature using TCGAdata topredict
overall survival (OS) of colorectal cancer. We identified five microbial speciesthrough univariate Cox regression and refined the model with multivariateCoxregression and survival random forest algorithms. Based on the median score, weclassified samples into high- and low-risk groups, revealing significantlypoorerprognosis in the high-risk group (p < 0.01). Additionally, we found nosignifi-cant correlation between the signature and clinical factors such as age, sex, orTNM stage, but it retained independent prognostic value in multivariate analysis(p < 0.01). We also analyzed genomic mutations, with CSMD3 showingsignificant differences between risk groups. Differentially expressed genes (DEGs)were enriched in ion channels, especially calcium channels, and immune-relatedpathways. Copy number variation analysis revealed more amplifications inthehigh-risk group. Furthermore, immune cell infiltration analysis usingmultiplealgorithms highlighted significant differences between risk groups, particularlyinnaïve B cells, CD4+ T cells, and CD8+ T cells. Drug response analysis identifiedseveral drugs, including Gemcitabine and Sorafenib, with greater sensitivityinthe low-risk group. Our study provides a novel tool and insight into the utilization of intratumoral microbiota for colorectal cancer.