Value of Serum NEUROG1 Methylation for the Detection of Advanced Adenomas and Colorectal Cancer
by
Olalla Otero-Estévez 1,2, María Gallardo-Gomez 1,2
, María Páez de la Cadena 1,2, Francisco Javier Rodríguez-Berrocal 1,2, Joaquín Cubiella 3, Vicent Hernandez Ramirez 4, Laura García-Nimo 5 and Loretta De Chiara 1,2,*
Olalla Otero-Estévez 1,2, María Gallardo-Gomez 1,2, María Páez de la Cadena 1,2, Francisco Javier Rodríguez-Berrocal 1,2, Joaquín Cubiella 3, Vicent Hernandez Ramirez 4, Laura García-Nimo 5 and Loretta De Chiara 1,2,*
1
Department of Biochemistry, Genetics and Immunology, University of Vigo, 36310 Vigo, Spain
2
Centro de Investigaciones Biomédicas, Centro Singular de Investigación de Galicia, University of Vigo, 36310 Vigo, Spain
3
Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, Instituto de Investigación Biomédica Galicia Sur, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 32005 Ourense, Spain
4
Department of Gastroenterology, Xerencia de Xestión Integrada de Vigo, Instituto de Investigación Biomédica Galicia Sur, 36213 Vigo, Spain
5
Department of Clinical Analysis, Complexo Hospitalario Universitario de Ourense, Instituto de Investigación Biomédica Galicia Sur, 32005 Ourense, Spain
*
Author to whom correspondence should be addressed.
Diagnostics 2020, 10(7), 437; https://doi.org/10.3390/diagnostics10070437
Received: 27 May 2020 / Revised: 23 June 2020 / Accepted: 26 June 2020 / Published: 28 June 2020
(This article belongs to the Special Issue Novel Approaches in the Diagnosis of Primary and Secondary Disease within Colorectal Cancer)
Aberrant DNA methylation detected in liquid biopsies is a promising approach for colorectal cancer (CRC) detection, including premalignant advanced adenomas (AA). We evaluated the diagnostic capability of serum NEUROG1 methylation for the detection of AA and CRC. A CpG island in NEUROG1 promoter was assessed by bisulfite pyrosequencing in a case-control cohort to select optimal CpGs. Selected sites were evaluated through a nested methylation-specific qPCR custom assay in a screening cohort of 504 asymptomatic family-risk individuals. Individuals with no colorectal findings and benign pathologies showed low serum NEUROG1 methylation, similar to non-advanced adenomas. Contrarily, individuals bearing AA or CRC (advanced neoplasia—AN), exhibited increased NEUROG1 methylation. Using >1.3518% as NEUROG1 cut-off (90.60% specificity), 33.33% of AN and 32.08% of AA were identified, detecting 50% CRC cases. Nonetheless, the combination of NEUROG1 with fecal immunochemical test (FIT), together with age and gender through a multivariate logistic regression resulted in an AUC = 0.810 for AN, and 0.796 for AA, detecting all cancer cases and 35–47% AA (specificity 98–95%). The combination of NEUROG1 methylation with FIT, age and gender demonstrated a convenient performance for the detection of CRC and AA, providing a valuable tool for CRC screening programs in asymptomatic individuals.
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Keywords:
DNA methylation; NEUROG1; colorectal cancer; advanced adenomas; screening; serum biomarker; FIT
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MDPI and ACS Style
Otero-Estévez, O.; Gallardo-Gomez, M.; Páez de la Cadena, M.; Rodríguez-Berrocal, F.J.; Cubiella, J.; Hernandez Ramirez, V.; García-Nimo, L.; De Chiara, L. Value of Serum NEUROG1 Methylation for the Detection of Advanced Adenomas and Colorectal Cancer. Diagnostics 2020, 10, 437.
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