DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation.

Abstract

BACKGROUND:

Esophageal cancer (ECa) is associated with high mortality, mostly due to late diagnosis, precluding curativeintent surgery. Hence, neoadjuvant chemoradiation (ChRT) is recommended in most patients regardless of histological subtype. A proportion of these patients, however, achieve complete disease remission and might be spared of radical surgery. The lack of reliable, minimally invasive biomarkers able to detect post-ChRT disease persistence is, nonetheless, a major drawback. We have previously shown that miRNA promotor methylation enables accurate cancer detection in tissues and liquid biopsies but has been seldom explored in ECa patients.

AIMS:

Herein, we sought to unveil and validate novel candidate biomarkers able to detect ECa prior and post ChRT.

MATERIALS AND METHODS:

Promoter methylation of miR129-2, miR124-3 and ZNF569 was assessed, using quantitative methylation-specific PCR (qMSP), in tissue samples from normal esophagus, treatment-naïve and post-ChRT ECa, as well as in liquid biopsies from ECa patients.

RESULTS:

All genes disclosed significantly different promoter methylation levels between ECa and normal esophagus, accurately detecting post-ChRT disease, especially for adenocarcinoma. Remarkably, miR129-2me /ZNF569me methylation panel identified ECa in liquid samples with 53% sensitivity and 87% specificity.

DISCUSSION:

MiR129-2me , miR124-3me and ZNF569me accurately discriminate ECa, either pre- or post-ChRT, from normal tissue, enabling ECa detection. Furthermore, circulalting methylation-based biomarkers are promising minimally invasive tools to detect post-ChRT residual ECa.

CONCLUSION:

Overall, our results encourage the use of miRNA methylation biomarkers as accurate ECa detection tools as a novel approach for ChRT response monitoring.

• Authors: Catarina Macedo-Silva, Vera Constâncio, Vera Miranda-Gonçalves, Pedro Leite-Silva, Sofia Salta, João Lobo, Rita Guimarães, Carina Carvalho-Maia, Davide Gigliano, Mónica Farinha, Olga Sousa, Rui Henrique, Carmen Jerónimo
• Journal: Cancer medicine (Cancer Med) Vol. 12 Issue 7 Pg. 8777-8788 (04 2023) ISSN: 2045-7634 [Electronic] United States
• PMID: 36670548 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• MicroRNAs
• Genetic Markers
• Biomarkers, Tumor
• ZNF569 protein, human
• Repressor Proteins
• Mirn129 microRNA, human

Topics

• Humans
• DNA Methylation
• Neoadjuvant Therapy
• MicroRNAs (genetics)
• Esophageal Neoplasms (diagnosis, genetics, therapy)
• Genetic Markers
• Biomarkers, Tumor (genetics)
• Repressor Proteins (genetics)