A DNA methylation-based test for esophageal cancer detection

Sofia Salta,Mónica Farinha,Olga Sousa,Rita Guimarães,Carmen Jerónimo,Nair Lopes,Vera Miranda-Gonçalves,Rui Henrique,Davide Gigliano,Catarina Macedo-Silva

doi:10.1186/s40364-020-00248-7

Abstract

BackgroundEsophageal cancer (ECa) is the 7th most incident cancer and the 6th leading cause of cancer-related death. Most patients are diagnosed with locally advanced or metastatic disease, enduring poor survival. Biomarkers enabling early cancer detection may improve patient management, treatment effectiveness, and survival, are urgently needed. In this context, epigenetic-based biomarkers such as DNA methylation are potential candidates.MethodsHerein, we sought to identify and validate DNA methylation-based biomarkers for early detection and prediction of response to therapy in ECa patients. Promoter methylation levels were assessed in a series of treatment-naïve ECa, post-neoadjuvant treatment ECa, and normal esophagus tissues, using quantitative methylation-specific PCR for COL14A1, GPX3, and ZNF569.ResultsZNF569 methylation (ZNF569me) levels significantly differed between ECa and normal samples (p < 0.001). Moreover, COL14A1 methylation (COL14A1me) and GPX3 methylation (GPX3me) levels discriminated adenocarcinomas and squamous cell carcinomas, respectively, from normal samples (p = 0.002 and p = 0.009, respectively). COL14A1me & ZNF569me accurately identified adenocarcinomas (82.29%) whereas GPX3me & ZNF569me identified squamous cell carcinomas with 81.73% accuracy. Furthermore, ZNF569me and GPX3me levels significantly differed between normal and pre-treated ECa.ConclusionThe biomarker potential of a specific panel of methylated genes for ECa was confirmed. These might prove useful for early detection and might allow for the identification of minimal residual disease after adjuvant therapy.

Highlights

Esophageal cancer (ECa) is the 7th most incident cancer and the 6th leading cause of cancer-related death
Based on the literature evidence, we aimed to identify and validate methylome alterations that might constitute biomarkers for early detection, as well as identification of minimal residual disease after neoadjuvant treatment, eventually precluding the need for esophagectomy
Promoter methylation levels of three genes selected [16, 17] Glutathione Peroxidase 3 (GPX3), Collagen Type XIV alpha chain (COL14A1), and Zinc finger protein 569 (ZNF569) - were tested in a series of ECa and normal esophageal tissues

Summary

Introduction

Esophageal cancer (ECa) is the 7th most incident cancer and the 6th leading cause of cancer-related death. Biomarkers enabling early cancer detection may improve patient management, treatment effectiveness, and survival, are urgently needed. In this context, epigenetic-based biomarkers such as DNA methylation are potential candidates. Surgery is often associated with decreased QoL due to complications and comorbidities [7, 8] Epigenetic alterations, including their key players, have emerged as promising biomarkers for ECa. Among those, gene methylation is the most extensively studied epigenetic modification. Promoter methylation of specific genes might be used to discriminate normal from cancerous esophageal cells, enabling the detection of disease at early stages, increasing the likelihood of curative treatment. The importance of these alterations is further highlighted by the numerous reports correlating aberrant DNA methylation with ECa patient prognosis [14, 15]

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