# Colorectal microenvironment determines the prognosis of colorectal cancer

## TL;DR

This study shows that the health of the colorectal microenvironment can predict cancer recurrence and survival, suggesting that maintaining a healthy gut environment may improve outcomes.

## Contribution

The study introduces a novel method to classify colorectal cancer patients based on tumor-supportive or healthy microenvironments using RNA sequencing data.

## Key findings

- Patients with tumor-supportive microenvironments had significantly worse 5-year survival rates.
- Tumor-supportive microenvironments showed shared microbiome composition and reduced metabolic pathway activity.
- Single-cell RNA sequencing revealed specific cell interactions in tumor-supportive environments.

## Abstract

Here we aimed to evaluate the feasibility of distinguishing colorectal microenvironments that support cancer cell growth from those that do not. We hypothesized that patients whose non-tumor-bearing tissue (NBT) obtained from the furthest margins of resected cancer specimens resembled the tumor had a poorer prognosis. Patients with colorectal cancer were divided into groups with tumor-supportive (TSM) or healthy microenvironments using bulk RNA sequencing data from 273 paired NBT and tumor samples. Patients in the TSM group exhibited significantly poorer 5-year recurrence-free survival and overall survival compared with those in the healthy microenvironment group. Pathway and 16S rRNA sequencing analyses revealed that NBT and tumors from the TSM group shared a microbiome composition, along with decreased pathway activity related to microvilli maintenance and flavonoid or vitamin metabolic processes. Single-cell RNA sequencing uncovered upregulated interactions between IL1Bhigh neutrophils and OLFM4+ epithelial cells in NBTs from the TSM group, as well as organized microniches in TSM tumors, featuring interactions between EMP1high epithelial cells, IL1Bhigh neutrophils and GZMKhigh CD8+ T cells. Collectively, the colorectal microenvironment can serve as a prognostic biomarker to effectively predict cancer invasiveness and tumor-promoting inflammation. Maintaining a healthy colorectal mucosal microenvironment, potentially through dietary intervention, is crucial.

Colorectal cancer (CRC) is a complex disease with varied genetic and environmental factors. Current genomic markers help to predict treatment outcomes for advanced cases but not for early-stage CRC. About 30–40% of CRC cases return after surgery, indicating a need for better predictive tools. Researchers explored using normal-looking tissue near tumors as a potential marker for recurrence. This study involved 273 patients with stage II or III CRC who underwent surgery. Researchers used RNA sequencing to analyze both the tumor and the nearby normal tissues. They identified specific genes that were more active in tumors and used these to classify patients into two groups: those with a tumor-supportive environment and those with a healthier environment. The results showed that patients with tumor-like features in their normal tissue had worse survival rates. This suggests that the surrounding tissue’s condition can predict cancer recurrence.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.