Evaluating the utility of ZNF331 promoter methylation as a prognostic and predictive marker in stage III colon cancer: results from CALGB 89803 (Alliance)

Autor: Elizabeth S. Nakasone, Tyler J. Zemla, Ming Yu, She Yu Lin, Fang-Shu Ou, Kelly Carter, Federico Innocenti, Leonard Saltz, William M. Grady, Stacey A. Cohen
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Epigenetics, Vol 19, Iss 1 (2024)
Druh dokumentu: article
ISSN: 15592294
1559-2308
1559-2294
DOI: 10.1080/15592294.2024.2349980
Popis: While epigenomic alterations are common in colorectal cancers (CRC), few epigenomic biomarkers that risk-stratify patients have been identified. We thus sought to determine the potential of ZNF331 promoter hypermethylation (mZNF331) as a prognostic and predictive marker in colon cancer. We examined the association of mZNF331 with clinicopathologic features, relapse, survival, and treatment efficacy in patients with stage III colon cancer treated within a randomized adjuvant chemotherapy trial (CALGB/Alliance89803). Residual tumour tissue was available for genomic DNA extraction and methylation analysis for 385 patients. ZNF331 promoter methylation status was determined by bisulphite conversion and fluorescence-based real-time polymerase chain reaction. Kaplan-Meier estimator and Cox proportional hazard models were used to assess the prognostic and predictive role of mZNF331 in this well-annotated dataset, adjusting for clinicopathologic features and standard molecular markers. mZNF331 was observed in 267/385 (69.4%) evaluable cases. Histopathologic features were largely similar between patients with mZNF331 compared to unmethylated ZNF331 (unmZNFF31). There was no significant difference in disease-free or overall survival between patients with mZNF331 versus unmZNF331 colon cancers, even when adjusting for clinicopathologic features and molecular marker status. Similarly, there was no difference in disease-free or overall survival across treatment arms when stratified by ZNF331 methylation status. While ZNF331 promoter hypermethylation is frequently observed in CRC, our current study of a small subset of patients with stage III colon cancer suggests limited applicability as a prognostic marker. Larger studies may provide more insight and clarity into the applicability of mZNF331 as a prognostic and predictive marker.
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