DNA methylation profiling enables accurate classification of nonductal primary pancreatic neoplasms Journal Article
| Authors: | Verschuur, A. V. D.; Hackeng, W. M.; Westerbeke, F.; Benhamida, J. K.; Basturk, O.; Selenica, P.; Raicu, G. M.; Molenaar, I. Q.; van Santvoort, H. C.; Daamen, L. A.; Klimstra, D. S.; Yachida, S.; Luchini, C.; Singhi, A. D.; Geisenberger, C.; Brosens, L. A. A. |
| Article Title: | DNA methylation profiling enables accurate classification of nonductal primary pancreatic neoplasms |
| Abstract: | Background & Aims: Cytologic and histopathologic diagnosis of non-ductal pancreatic neoplasms can be challenging in daily clinical practice, whereas it is crucial for therapy and prognosis. The cancer methylome is successfully used as a diagnostic tool in other cancer entities. Here, we investigate if methylation profiling can improve the diagnostic work-up of pancreatic neoplasms. Methods: DNA methylation data were obtained for 301 primary tumors spanning 6 primary pancreatic neoplasms and 20 normal pancreas controls. Neural Network, Random Forest, and extreme gradient boosting machine learning models were trained to distinguish between tumor types. Methylation data of 29 nonpancreatic neoplasms (n = 3708) were used to develop an algorithm capable of detecting neoplasms of non-pancreatic origin. Results: After benchmarking 3 state-of-the-art machine learning models, the random forest model emerged as the best classifier with 96.9% accuracy. All classifications received a probability score reflecting the confidence of the prediction. Increasing the score threshold improved the random forest classifier performance up to 100% with 87% of samples with scores surpassing the cutoff. Using a logistic regression model, detection of nonpancreatic neoplasms achieved an area under the curve of >0.99. Analysis of biopsy specimens showed concordant classification with their paired resection sample. Conclusions: Pancreatic neoplasms can be classified with high accuracy based on DNA methylation signatures. Additionally, non-pancreatic neoplasms are identified with near perfect precision. In summary, methylation profiling can serve as a valuable adjunct in the diagnosis of pancreatic neoplasms with minimal risk for misdiagnosis, even in the pre-operative setting. © 2024 The Author(s) |
| Keywords: | immunohistochemistry; controlled study; human tissue; aged; middle aged; primary tumor; gene cluster; gene mutation; major clinical study; genetics; histopathology; area under the curve; validation process; bone metastasis; pancreatic neoplasms; quality control; classification; tumor volume; cohort analysis; pathology; retrospective study; dna methylation; neuroendocrine tumor; patient care; liver metastasis; diagnosis; pancreas tumor; benchmarking; logistic regression analysis; acinar cell carcinoma; beta catenin; dna extraction; liver biopsy; tumor classification; nerve cell network; receiver operating characteristic; classification algorithm; pancreas islet cell carcinoma; vimentin; common acute lymphoblastic leukemia antigen; solid pseudopapillary tumor; pancreatic ductal adenocarcinoma; diagnostic test accuracy study; pancreatic ductal carcinoma; fine needle aspiration biopsy; pancreatic neuroendocrine tumor; pancreatoblastoma; machine learning; humans; human; male; female; article; whole genome sequencing; solid pseudopapillary neoplasms; random forest; edotreotide ga 68 |
| Journal Title: | Clinical Gastroenterology and Hepatology |
| Volume: | 22 |
| Issue: | 6 |
| ISSN: | 1542-3565 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2024-06-01 |
| Start Page: | 1245 |
| End Page: | 1254.e10 |
| Language: | English |
| DOI: | 10.1016/j.cgh.2024.02.007 |
| PUBMED: | 38382726 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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