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, achiev...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-04-01
|
| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.5623 |
| _version_ | 1797838402928771072 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Catarina Macedo‐Silva |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T15:41:20Z |
| format | Article |
| id | doaj.art-d970b954e26b4a219791784a6f9bb2cf |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-09T15:41:20Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-d970b954e26b4a219791784a6f9bb2cf2023-04-27T10:12:44ZengWileyCancer Medicine2045-76342023-04-011278777878810.1002/cam4.5623DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiationCatarina Macedo‐Silva0Vera Constâncio1Vera Miranda‐Gonçalves2Pedro Leite‐Silva3Sofia Salta4João Lobo5Rita Guimarães6Carina Carvalho‐Maia7Davide Gigliano8Mónica Farinha9Olga Sousa10Rui Henrique11Carmen Jerónimo12Cancer Biology & Epigenetics Group, Research Center of IPO Porto (CI‐IPOP)/RISE@CI‐IPOP (Health Research Network) Portuguese Oncology Institute of Porto (IPO‐Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC) Porto PortugalCancer Biology & Epigenetics Group, Research Center of IPO Porto (CI‐IPOP)/RISE@CI‐IPOP (Health Research Network) Portuguese Oncology Institute of Porto (IPO‐Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC) Porto PortugalCancer Biology & Epigenetics Group, Research Center of IPO Porto (CI‐IPOP)/RISE@CI‐IPOP (Health Research Network) Portuguese Oncology Institute of Porto (IPO‐Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC) Porto PortugalCancer Epidemiology Group, Research Center & Department of Epidemiology of IPO Porto (CI‐IPOP)/RISE@CI‐IPOP (Health Research Network) Portuguese Oncology Institute of Porto (IPO‐Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC) Porto PortugalCancer Biology & Epigenetics Group, Research Center of IPO Porto (CI‐IPOP)/RISE@CI‐IPOP (Health Research Network) Portuguese Oncology Institute of Porto (IPO‐Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC) Porto PortugalCancer Biology & Epigenetics Group, Research Center of IPO Porto (CI‐IPOP)/RISE@CI‐IPOP (Health Research Network) Portuguese Oncology Institute of Porto (IPO‐Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC) Porto PortugalCancer Biology & Epigenetics Group, Research Center of IPO Porto (CI‐IPOP)/RISE@CI‐IPOP (Health Research Network) Portuguese Oncology Institute of Porto (IPO‐Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC) Porto PortugalCancer Biology & Epigenetics Group, Research Center of IPO Porto (CI‐IPOP)/RISE@CI‐IPOP (Health Research Network) Portuguese Oncology Institute of Porto (IPO‐Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC) Porto PortugalCancer Biology & Epigenetics Group, Research Center of IPO Porto (CI‐IPOP)/RISE@CI‐IPOP (Health Research Network) Portuguese Oncology Institute of Porto (IPO‐Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC) Porto PortugalCancer Biology & Epigenetics Group, Research Center of IPO Porto (CI‐IPOP)/RISE@CI‐IPOP (Health Research Network) Portuguese Oncology Institute of Porto (IPO‐Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC) Porto PortugalDepartment of Radiation Oncology Portuguese Oncology Institute of Porto Porto PortugalCancer Biology & Epigenetics Group, Research Center of IPO Porto (CI‐IPOP)/RISE@CI‐IPOP (Health Research Network) Portuguese Oncology Institute of Porto (IPO‐Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC) Porto PortugalCancer Biology & Epigenetics Group, Research Center of IPO Porto (CI‐IPOP)/RISE@CI‐IPOP (Health Research Network) Portuguese Oncology Institute of Porto (IPO‐Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC) Porto PortugalAbstract 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.https://doi.org/10.1002/cam4.5623esophageal cancerliquid biopsiesmethylation biomarkersmiRNAsneoadjuvant chemoradiation |
| spellingShingle | 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 DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation Cancer Medicine esophageal cancer liquid biopsies methylation biomarkers miRNAs neoadjuvant chemoradiation |
| title | DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation |
| title_full | DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation |
| title_fullStr | DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation |
| title_full_unstemmed | DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation |
| title_short | DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation |
| title_sort | dna methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation |
| topic | esophageal cancer liquid biopsies methylation biomarkers miRNAs neoadjuvant chemoradiation |
| url | https://doi.org/10.1002/cam4.5623 |
| work_keys_str_mv | AT catarinamacedosilva dnamethylationbiomarkersaccuratelydetectesophagealcancerpriorandpostneoadjuvantchemoradiation AT veraconstancio dnamethylationbiomarkersaccuratelydetectesophagealcancerpriorandpostneoadjuvantchemoradiation AT veramirandagoncalves dnamethylationbiomarkersaccuratelydetectesophagealcancerpriorandpostneoadjuvantchemoradiation AT pedroleitesilva dnamethylationbiomarkersaccuratelydetectesophagealcancerpriorandpostneoadjuvantchemoradiation AT sofiasalta dnamethylationbiomarkersaccuratelydetectesophagealcancerpriorandpostneoadjuvantchemoradiation AT joaolobo dnamethylationbiomarkersaccuratelydetectesophagealcancerpriorandpostneoadjuvantchemoradiation AT ritaguimaraes dnamethylationbiomarkersaccuratelydetectesophagealcancerpriorandpostneoadjuvantchemoradiation AT carinacarvalhomaia dnamethylationbiomarkersaccuratelydetectesophagealcancerpriorandpostneoadjuvantchemoradiation AT davidegigliano dnamethylationbiomarkersaccuratelydetectesophagealcancerpriorandpostneoadjuvantchemoradiation AT monicafarinha dnamethylationbiomarkersaccuratelydetectesophagealcancerpriorandpostneoadjuvantchemoradiation AT olgasousa dnamethylationbiomarkersaccuratelydetectesophagealcancerpriorandpostneoadjuvantchemoradiation AT ruihenrique dnamethylationbiomarkersaccuratelydetectesophagealcancerpriorandpostneoadjuvantchemoradiation AT carmenjeronimo dnamethylationbiomarkersaccuratelydetectesophagealcancerpriorandpostneoadjuvantchemoradiation |