Daxx Variation as a Potential Predictive Marker of the Therapeutic Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

TL;DR

This study identifies Daxx as a potential biomarker to predict how well patients with rectal cancer respond to a specific treatment called neoadjuvant chemoradiotherapy.

Contribution

The study discovers that Daxx expression is a novel predictive marker for treatment response in rectal cancer patients.

Findings

Eleven genes, including Daxx, showed copy number variations in tumor samples.

High Daxx expression in sensitive response groups correlates with better treatment outcomes and disease-free survival.

Daxx levels change after treatment, indicating its potential as a predictive biomarker.

Abstract

The response to neoadjuvant chemoradiotherapy (NACRT) for locally advanced rectal cancer (LARC) varies from achieving a complete pathological response to encountering resistance to treatment. Therefore, biomarkers for predicting the NACRT responses should be identified. This prospective study aimed to identify key genomic biomarkers as the predictors of the NACRT response with LARC.

Overall, 67 patients with LARC treated with NACRT and proctectomy were divided into two groups based on the tumor regression grade (TRG) for identifying key biomarkers. Patients with a TRG of 0 or 1 were assigned to the sensitive response group, and patients with a TRG of 2 or 3 were the resistant response group. Twenty‐nine postsurgical tumor samples were collected for whole exome sequencing (WES) to identify genomic variation biomarkers. The other 38 pairs of tumor specimens from pretreatment and postsurgery samples were evaluated by immunohistochemistry (IHC) to examine the biomarker features.

In the WES subcohort, 11 genes showed copy number variation, including FNKBIA, ARID1A, CCND2, CDK4, LYN, MDM2, RAD51B, RARA, SPEN, STAT3, and Daxx, which has the highest copy number variation. For the IHC subcohort, Daxx was initially highly expressed in the nuclei of tumor cells, particularly in the sensitive response group, while varying its expression after NACRT, demonstrating that Daxx levels were related to treatment responses and the survival benefit, especially a better disease‐free survival (DFS).

We identified multiple genomic variations between sensitive and resistant responders and verified that Daxx is a potential predictive biomarker of the response to NACRT in LARC.

Multiple genomic variations between sensitive and resistant responders to NACRT in LARC were found. High Daxx expression is a potential predictive biomarker for the response to NACRT and is associated with a favorable clinical prognosis.

Figures