Evaluating the utility of ZNF331 promoter methylation as a prognostic and predictive marker in stage III colon cancer: Results from CALGB 89803 (Alliance) Journal Article
| Authors: | Nakasone, E. S.; Zemla, T. J.; Yu, M.; Lin, S. Y.; Ou, F. S.; Carter, K.; Innocenti, F.; Saltz, L.; Grady, W. M.; Cohen, S. A. |
| Article Title: | Evaluating the utility of ZNF331 promoter methylation as a prognostic and predictive marker in stage III colon cancer: Results from CALGB 89803 (Alliance) |
| Abstract: | 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. © 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. |
| Keywords: | immunohistochemistry; adult; cancer survival; controlled study; human tissue; protein expression; aged; middle aged; unclassified drug; major clinical study; methylation; overall survival; promoter region; genetics; clinical trial; histopathology; mortality; fluorouracil; disease free survival; cancer staging; neoplasm staging; polymerase chain reaction; biological marker; metabolism; progression free survival; randomized controlled trial; colonic neoplasms; transcription factor; pathology; protein p53; tumor marker; dna methylation; risk factor; transcription factors; irinotecan; molecular marker; minimal residual disease; cpg island; promoter regions, genetic; biomarker; folinic acid; colon cancer; mismatch repair; adjuvant chemotherapy; colon tumor; microsatellite instability; real time polymerase chain reaction; phase 3 clinical trial; k ras protein; zinc finger protein; dna extraction; mismatch repair protein; b raf kinase; disease specific survival; genomic dna; predictive marker; cancer prognosis; humans; prognosis; human; male; female; article; epigenetic factors; biomarkers, tumor; stage iii colon cancer; calgb 89803 (alliance); znf331; trefoil factor-3; zinc finger protein 331; tff3 protein, human; trefoil factor 3 |
| Journal Title: | Epigenetics |
| Volume: | 19 |
| Issue: | 1 |
| ISSN: | 1559-2294 |
| Publisher: | Landes Bioscience |
| Date Published: | 2024-01-01 |
| Start Page: | 2349980 |
| Language: | English |
| DOI: | 10.1080/15592294.2024.2349980 |
| PUBMED: | 38716804 |
| PROVIDER: | scopus |
| PMCID: | PMC11085945 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
