A DNA methylation-based test for esophageal cancer detection
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RESEARCH
Open Access
A DNA methylation-based test for esophageal cancer detection Sofia Salta1, Catarina Macedo-Silva1, Vera Miranda-Gonçalves1, Nair Lopes1, Davide Gigliano1,2, Rita Guimarães1,2, Mónica Farinha1,2, Olga Sousa3, Rui Henrique1,2,4 and Carmen Jerónimo1,4*
Abstract Background: Esophageal 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. Methods: Herein, 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 treatmentnaïve ECa, post-neoadjuvant treatment ECa, and normal esophagus tissues, using quantitative methylation-specific PCR for COL14A1, GPX3, and ZNF569. Results: ZNF569 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. Conclusion: The 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. Keywords: Esophageal Cancer, DNA methylation, Early detection; treatment response
Background Esophageal cancer (ECa) is the 7th most common malignancy and the 6th cause of cancer-related mortality worldwide [1]. ECa comprises two main histological subtypes: adenocarcinoma and squamous cell carcinoma, * Correspondence: [email protected]; [email protected] 1 Cancer Biology & Epigenetics Group – Research Center, Portuguese Oncology Institute of Porto, Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal 4 Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar– University of Porto , Rua de Jorge Viterbo Ferreira, 228, Porto 4050-313, Portugal Full list of author information is available at the end of the article
the most prevalent type [2]. Although therapeutic improvements have increased ECa survival rates [3], curative-intent treatment options remain limited to surgery, chemotherapy (ChT), and radiotherapy (RT), either alone or in trimodal therapy [4]. Furthermore, most tumors are diagnosed at an advanced stage, entailing very low 5-year survival rates, ranging f
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