학술논문
Early detection of the major male cancer types in blood-based liquid biopsies using a DNA methylation panel.
Document Type
Academic Journal
Author
Constâncio V; Cancer Biology & Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), LAB 3, F Bdg, 1st floor Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.; Master in Oncology, Institute of Biomedical Sciences Abel Salazar-University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal.; Nunes SP; Cancer Biology & Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), LAB 3, F Bdg, 1st floor Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.; Moreira-Barbosa C; Cancer Biology & Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), LAB 3, F Bdg, 1st floor Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.; Freitas R; Urology Clinic, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.; Oliveira J; Urology Clinic, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.; Pousa I; Lung Cancer Clinic and Department of Medical Oncology, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.; Oliveira J; Lung Cancer Clinic and Department of Medical Oncology, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.; Soares M; Lung Cancer Clinic and Department of Medical Oncology, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.; Dias CG; Digestive Tract Pathology Clinic and Surgical Oncology, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.; Dias T; Digestive Tract Pathology Clinic and Surgical Oncology, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.; Antunes L; Department of Epidemiology, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.; Henrique R; Cancer Biology & Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), LAB 3, F Bdg, 1st floor Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.; Department of Pathology, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.; Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar-University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal.; Jerónimo C; Cancer Biology & Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), LAB 3, F Bdg, 1st floor Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal. carmenjeronimo@ipoporto.min-saude.pt.; Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar-University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal. carmenjeronimo@ipoporto.min-saude.pt.
Source
Publisher: BiomedCentral Country of Publication: Germany NLM ID: 101516977 Publication Model: Electronic Cited Medium: Internet ISSN: 1868-7083 (Electronic) Linking ISSN: 18687075 NLM ISO Abbreviation: Clin Epigenetics Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Lung (LC), prostate (PCa) and colorectal (CRC) cancers are the most incident in males worldwide. Despite recent advances, optimal population-based cancer screening methods remain an unmet need. Due to its early onset, cancer specificity and accessibility in body fluids, aberrant DNA promoter methylation might be a valuable minimally invasive tool for early cancer detection. Herein, we aimed to develop a minimally invasive methylation-based test for simultaneous early detection of LC, PCa and CRC in males, using liquid biopsies.
Results: Circulating cell-free DNA was extracted from 102 LC, 121 PCa and 100 CRC patients and 136 asymptomatic donors' plasma samples. Sodium-bisulfite modification and whole-genome amplification was performed. Promoter methylation levels of APCme , FOXA1 me , GSTP1 me , HOXD3 me , RARβ2 me , RASSF1A me , SEPT9 me and SOX17 me were assessed by multiplex quantitative methylation-specific PCR. SEPT9 me and SOX17 me were the only biomarkers shared by all three cancer types, although they detected CRC with limited sensitivity. A "PanCancer" panel (FOXA1 me , RARβ2 me and RASSF1A me ) detected LC and PCa with 64% sensitivity and 70% specificity, complemented with "CancerType" panel (GSTP1 me and SOX17 me ) which discriminated between LC and PCa with 93% specificity, but with modest sensitivity. Moreover, a HOXD3 me and RASSF1A me panel discriminated small cell lung carcinoma from non-small cell lung carcinoma with 75% sensitivity, 88% specificity, 6.5 LR+ and 0.28 LR-. An APC me and RASSF1A me panel independently predicted disease-specific mortality in LC patients.
Conclusions: We concluded that a DNA methylation-based test in liquid biopsies might enable minimally invasive screening of LC and PCa, improving patient compliance and reducing healthcare costs. Moreover, it might assist in LC subtyping and prognostication.
Results: Circulating cell-free DNA was extracted from 102 LC, 121 PCa and 100 CRC patients and 136 asymptomatic donors' plasma samples. Sodium-bisulfite modification and whole-genome amplification was performed. Promoter methylation levels of APC
Conclusions: We concluded that a DNA methylation-based test in liquid biopsies might enable minimally invasive screening of LC and PCa, improving patient compliance and reducing healthcare costs. Moreover, it might assist in LC subtyping and prognostication.