DNA strand transforming into a flower

Decoding Cancer's Response: Can DNA Methylation Guide Rectal Cancer Treatment?

Lena Voss in Health & Wellness July 2025 • 4 min read.

"New research explores how analyzing tissue DNA methylation could help personalize treatment decisions for rectal cancer patients after neoadjuvant therapy."

For individuals diagnosed with rectal cancer, neoadjuvant chemo-radiotherapy plays a crucial role in minimizing the likelihood of local recurrence following surgery. While this treatment demonstrates effectiveness, approximately 20% of patients exhibit a complete pathological response, marked by the absence of residual primary tumor in pathological specimens. This group often experiences excellent disease-free survival rates, raising the possibility of avoiding surgery altogether.

The challenge lies in the absence of reliable biomarkers to guide clinical decisions, specifically in determining which patients can safely pursue a 'watch and wait' approach after neoadjuvant therapy. Recent studies suggest that alterations in DNA methylation may serve as predictive biomarkers for treatment response in solid tumors, including breast and rectal cancers.

A new study seeks to discover highly predictable methylation markers for chemoradiation response. The goal is to refine surgical strategies for a significant number of patients, potentially offering conservative approaches like local excision or even non-operative management without compromising prognosis. This could mark a significant step towards personalized rectal cancer treatment.

DNA Methylation: A Key to Predicting Treatment Response

DNA strand transforming into a flower

The study retrospectively analyzed patients diagnosed with rectal cancer between 2006 and 2016, who underwent chemoradiation therapy followed by resection. Researchers collected data on disease recurrence and clinical parameters from patient medical records, while expert pathologists evaluated tumor specimens using tumor regression scores (TRS). Tissue samples were then analyzed for DNA methylation patterns using the Illumina EPIC array.

The research team enrolled 51 patients, excluding four with metastatic disease. Post-surgical follow-up ranged from 3 months to 10 years (median 36 months). Higher disease recurrence rates correlated with patients who showed poor therapy response (TRS 3) compared to those with complete or moderate responses (TRS 0-2). Liver and lungs were the most common sites of recurrence.

Normal: Baseline methylation levels in healthy tissue.
Non-response: Methylation profiles in patients showing minimal or no response to neoadjuvant treatment (TRS 3).
Partial response: Methylation patterns in patients with some tumor regression (TRS 2).
Very good response: Methylation profiles in patients demonstrating significant tumor regression (TRS 1).
Complete response: Methylation patterns in patients with no detectable residual tumor after treatment (TRS 0).

DNA methylation profiles identified 638 CpG sites with significantly different methylation levels (p < 10-4) between TRS 0 + 1, 2, and 3, indicating unique methylation patterns associated with treatment response. This suggests the potential to differentiate complete responders, intermediate responders, and non-responders based on their DNA methylation profiles.

Personalized Treatment on the Horizon

The study concludes that rectal cancer patients achieving complete pathological response after neoadjuvant therapy exhibit a significantly lower risk of disease recurrence following surgery. Resected tissue from this group displays a unique DNA methylation pattern, which could serve as a valuable biomarker in conjunction with clinical and imaging findings.

These findings support the 'watch and wait' approach, potentially sparing patients from unnecessary and morbid surgeries. Integrating DNA methylation analysis into treatment strategies could refine patient selection for non-operative management, leading to more personalized and effective care.

Further research is needed to validate these findings in larger cohorts and to develop standardized assays for clinical application. However, this study represents a promising step towards incorporating DNA methylation analysis into the clinical decision-making process for rectal cancer patients.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1093/annonc/mdx261.262, Alternate LINK

Title: Tissue Dna Methylation As A Tool For Clinical Decision Making After Neo-Adjuvant Treatment In Rectal Cancer

Subject: Oncology

Journal: Annals of Oncology

Publisher: Elsevier BV

Authors: Moshe Mishaeli, Liron Berkovich, Baruch Shpitz, Nasreen Hag-Yahiya, Walter Pulverer, Andreas Weinhäusel, Ronen Ghinea, Shmuel Avital

Published: 2017-06-01

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Everything You Need To Know

1

What is DNA Methylation and why is it important in this context?

DNA Methylation refers to the process where methyl groups attach to DNA, which can influence gene expression. In this context, alterations in DNA Methylation patterns may predict how a patient will respond to Neoadjuvant chemo-radiotherapy for Rectal Cancer. The study used the Illumina EPIC array to analyze tissue samples for these patterns. Different methylation profiles were observed in patients with Complete response (TRS 0), Very good response (TRS 1), Partial response (TRS 2), and Non-response (TRS 3). The significance lies in its potential to identify patients who may benefit from less aggressive treatments.

2

What is Neoadjuvant chemo-radiotherapy and what is its role in Rectal Cancer treatment?

Neoadjuvant chemo-radiotherapy is a treatment approach used for Rectal Cancer. It involves giving chemotherapy and radiation therapy before surgery. This aims to shrink the tumor, making it easier to remove surgically and decreasing the chance of the cancer returning. In the study, the effectiveness of this therapy was assessed by evaluating the presence of residual tumor in pathological specimens and assessing the response using Tumor Regression Scores (TRS). The study found that a significant portion of patients show complete pathological response after this therapy, suggesting a potential opportunity to personalize treatment.

3

What was the main goal of the study on Rectal Cancer?

The study focused on predicting treatment response in Rectal Cancer patients after Neoadjuvant chemo-radiotherapy. The study analyzed data from patients who underwent the therapy and subsequent resection. Researchers examined the correlation between DNA Methylation patterns in tumor tissue and the clinical outcomes, including disease recurrence and Tumor Regression Scores (TRS). The goal was to find specific DNA Methylation markers that could identify patients more likely to benefit from the treatment and potentially avoid or alter the surgical approach.

4

What are Tumor Regression Scores (TRS) and what do they indicate?

Tumor Regression Scores (TRS) are used to assess how well a patient's Rectal Cancer responds to Neoadjuvant chemo-radiotherapy. The scores range from 0 to 3, where TRS 0 indicates a complete response with no residual tumor, and TRS 3 indicates a non-response with minimal or no tumor regression. The study found distinct DNA Methylation patterns associated with different TRS categories, suggesting that DNA Methylation could predict the treatment response, enabling clinicians to tailor treatment decisions more effectively.

5

What does the 'watch and wait' approach mean, and how is it related to the study's findings?

A 'watch and wait' approach refers to a treatment strategy where surgery is avoided in patients with Rectal Cancer who show a complete pathological response after Neoadjuvant chemo-radiotherapy. Instead of immediate surgery, these patients are closely monitored for any signs of cancer recurrence. The study suggests that DNA Methylation patterns may identify those patients who are highly unlikely to experience disease recurrence. Identifying these patients could allow for a more conservative treatment strategy, potentially avoiding unnecessary surgery, and improving the patient's quality of life without compromising their prognosis.