Genome Methylation Accurately Predicts Neuroendocrine Tumor Origin: An Online Tool.
Clin Cancer Res
; 27(5): 1341-1350, 2021 03 01.
Article
em En
| MEDLINE
| ID: mdl-33355250
ABSTRACT
PURPOSE:
The primary origin of neuroendocrine tumor metastases can be difficult to determine by histopathology alone, but is critical for therapeutic decision making. DNA methylation-based profiling is now routinely used in the diagnostic workup of brain tumors. This has been enabled by the availability of cost-efficient array-based platforms. We have extended these efforts to augment histopathologic diagnosis in neuroendocrine tumors. EXPERIMENTALDESIGN:
Methylation data was compiled for 69 small intestinal, pulmonary, and pancreatic neuroendocrine tumors. These data were used to build a ridge regression calibrated random forest classification algorithm (neuroendocrine neoplasm identifier, NEN-ID). The model was validated during 3 × 3 nested cross-validation and tested in a local and an external cohort (n = 198 cases).RESULTS:
NEN-ID predicted the origin of tumor samples with high accuracy (>95%). In addition, the diagnostic approach was determined to be robust across a range of possible confounding experimental parameters, such as tumor purity and array quality. A software infrastructure and online user interface were built to make the model available to the scientific community.CONCLUSIONS:
This DNA methylation-based prediction model can be used in the workup for patients with neuroendocrine tumors of unknown primary. To facilitate validation and clinical implementation, we provide a user-friendly, publicly available web-based version of NEN-ID.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Biomarcadores Tumorais
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Regulação Neoplásica da Expressão Gênica
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Tumores Neuroendócrinos
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Metilação de DNA
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Neoplasias Intestinais
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Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article