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. 2020 Jun 28;10(7):437.
doi: 10.3390/diagnostics10070437.

Value of Serum NEUROG1 Methylation for the Detection of Advanced Adenomas and Colorectal Cancer

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 , Loretta De Chiara  1   2
Affiliations

Value of Serum NEUROG1 Methylation for the Detection of Advanced Adenomas and Colorectal Cancer

Olalla Otero-Estévez et al. Diagnostics (Basel). .

Abstract

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.

Keywords: DNA methylation; FIT; NEUROG1; advanced adenomas; colorectal cancer; screening; serum biomarker.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Study design flow-chart. FDR: first-degree relative; NCF: no colorectal findings; BEN: benign pathology; NAA: non-advanced adenomas; AA: advanced adenomas; CRC: colorectal cancer.
Figure 2
Figure 2
Representation of the CpG island analyzed located in the promoter of NEUROG1. The relative position of the 12 CpG sites is shown. Forward and reverse primers (solid arrows), and sequencing primer (dashed line) used for bisulphite pyrosequencing (B = biotin) is shown on the top of the figure. Forward and reverse primers (solid arrows), and probe (dashed line) used for the MS-qPCR is shown on the bottom of the figure.
See this image and copyright information in PMC

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