# Pre-Treatment SEPTIN9 Gene Methylation Ratio Predicts Tumor Response to Total Neoadjuvant Therapy in Patients with Locally Advanced Rectal Cancer

## TL;DR

This study shows that the SEPTIN9 gene methylation ratio before treatment can predict how well rectal cancer tumors will respond to therapy.

## Contribution

The study introduces SEPTIN9 gene methylation ratio as a novel pre-treatment predictor of tumor response to total neoadjuvant therapy in rectal cancer.

## Key findings

- Pre-treatment SEPTIN9 gene methylation ratio significantly correlates with tumor response to therapy (p = 0.033).
- SEPTIN9 methylation ratio correlates with tumor size (p = 0.001) and N stage (p = 0.040), but not T stage.

## Abstract

There are no reliable pre-treatment markers that predict tumor response to total neoadjuvant therapy in patients with locally advanced rectal cancer. The aim of this study is to evaluate the usefulness of pre-treatment SEPTIN9 gene methylation ratio as a predictor of tumor response to total neoadjuvant therapy and its correlation with tumor size and tumor stage in patients with locally advanced rectal cancer. Pre-treatment SEPTIN9 gene methylation ratio (p = 0.033) and tumor size (p = 0.026), but not tumor stage, significantly correlated with tumor response to total neoadjuvant therapy. Pre-treatment SEPTIN9 gene methylation ratio also correlated with N stage (p = 0.040) and tumor size (p = 0.001), but not with T stage (p = 0.846). Thus, pre-treatment SEPTIN9 gene methylation ratio correlates with tumor size and N stage and can predict tumor response to total neoadjuvant therapy in patients with locally advanced rectal cancer.

Background and objective: Multiple markers have been proposed, but there are no reliable pre-treatment markers that predict tumor response to total neoadjuvant therapy in patients with locally advanced rectal cancer. The objective of this study is to evaluate the usefulness of pre-treatment SEPTIN9 gene methylation ratio as a predictor of tumor response to total neoadjuvant therapy and its correlation with tumor size and tumor stage in patients with locally advanced rectal cancer. Methods: Patients with locally advanced rectal cancer (T3/4 and/or N+ histologically confirmed rectal cancer) undergoing total neoadjuvant therapy were included. Tumor size and tumor stage were determined by magnetic resonance. SEPTIN9 gene methylation in plasmatic cfDNA was analyzed by droplet digital PCR at the time of diagnosis. After completing total neoadjuvant therapy, tumor response was assessed by magnetic resonance and proctoscopy. The correlation between pre-treatment SEPTIN9 gene methylation ratio, tumor size, tumor stage and tumor response was analyzed. Results: 39 patients with locally advanced rectal cancer were included. Pre-treatment SEPTIN9 gene methylation ratio (p = 0.033) and tumor size (p = 0.026), but not tumor stage, significantly correlated with tumor response to total neoadjuvant therapy. Pre-treatment SEPTIN9 gene methylation ratio also correlated with N stage (p = 0.040) and tumor size (p = 0.001), but not with T stage (p = 0.846). Conclusions: Pre-treatment SEPTIN9 gene methylation ratio correlates with tumor size and N stage and can predict tumor response to total neoadjuvant therapy in patients with locally advanced rectal cancer.