# Combining the DNA methylation markers of circulating tumor cells with immune infiltrating cells to assess recurrence and prognosis and to suggest a therapeutic strategy in stage III-IV colorectal cancer

## TL;DR

This study identifies DNA methylation markers that predict cancer recurrence and prognosis in colorectal cancer patients and suggests personalized treatment strategies based on immune response.

## Contribution

The study introduces a novel risk model combining DNA methylation markers and immune infiltration data for predicting recurrence and prognosis in CRC.

## Key findings

- ZNF671 and ZNF132 are key methylation markers predictive of relapse and prognosis in CRC patients.
- High-risk patients have a significantly higher early relapse rate and lower Immunoscore.
- Methylation levels of ZNF671 and ZNF132 inversely correlate with Immunoscore, indicating potential for immunotherapy biomarkers.

## Abstract

Circulating tumor DNA (ctDNA) methylation markers show potential for early detection of cancer metastasis. This study aimed to identify ctDNA methylation markers predictive of recurrence and prognosis in colorectal cancer (CRC) patients, and to explore the influence of the tumor immune microenvironment on outcomes.

We analyzed 603 overlapping methylation markers from both plasma and tissue samples and developed a risk model to predict CRC recurrence and prognosis.

ZNF671 and ZNF132 were identified as key methylation markers. The model predicted relapse risk in stage III CRC patients with an AUC of 0.90 and prognosis in stage IV patients. High-risk patients exhibited a significantly higher early relapse rate (75.4% vs. 20%) and were more likely to have a low Immunoscore (IS), which correlates with poorer prognosis.

ZNF671 and ZNF132 methylation levels inversely correlate with Immunoscore and may serve as valuable biomarkers for CRC immunotherapy. These findings provide insights for improved prognostic evaluation and personalized treatment strategies.