Journal article
Functional Copy-Number Alterations as Diagnostic and Prognostic Biomarkers in Neuroendocrine Tumors
International journal of molecular sciences, Vol.25(14), 7532
07/09/2024
DOI: 10.3390/ijms25147532
PMCID: PMC11277019
PMID: 39062773
Abstract
Functional copy-number alterations (fCNAs) are DNA copy-number changes with concordant differential gene expression. These are less likely to be bystander genetic lesions and could serve as robust and reproducible tumor biomarkers. To identify candidate fCNAs in neuroendocrine tumors (NETs), we integrated chromosomal microarray (CMA) and RNA-seq differential gene-expression data from 31 pancreatic (pNETs) and 33 small-bowel neuroendocrine tumors (sbNETs). Tumors were resected from 47 early-disease-progression (<24 months) and 17 late-disease-progression (>24 months) patients. Candidate fCNAs that accurately differentiated these groups in this discovery cohort were then replicated using fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded (FFPE) tissues in a larger validation cohort of 60 pNETs and 82 sbNETs (52 early- and 65 late-disease-progression samples). Logistic regression analysis revealed the predictive ability of these biomarkers, as well as the assay-performance metrics of sensitivity, specificity, and area under the curve. Our results indicate that copy-number changes at chromosomal loci 4p16.3, 7q31.2, 9p21.3, 17q12, 18q21.2, and 19q12 may be used as diagnostic and prognostic NET biomarkers. This involves a rapid, cost-effective approach to determine the primary tumor site for patients with metastatic liver NETs and to guide risk-stratified therapeutic decisions.
Details
- Title: Subtitle
- Functional Copy-Number Alterations as Diagnostic and Prognostic Biomarkers in Neuroendocrine Tumors
- Creators
- Hayley Vaughn - University of IowaHeather Major - University of IowaEvangeline Kadera - University of Iowa Health CareKendall Keck - University of IowaTimothy Dunham - University of IowaQining Qian - University of IowaBartley BrownAaron Scott - University of Iowa Health CareAndrew M. Bellizzi - University of IowaTerry Braun - University of IowaPatrick Breheny - University of IowaDawn E. Quelle - University of IowaJames R. Howe - University of Iowa Health CareBenjamin Darbro - University of Iowa
- Resource Type
- Journal article
- Publication Details
- International journal of molecular sciences, Vol.25(14), 7532
- DOI
- 10.3390/ijms25147532
- PMID
- 39062773
- PMCID
- PMC11277019
- ISSN
- 1422-0067
- eISSN
- 1422-0067
- Language
- English
- Date published
- 07/09/2024
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Stead Family Department of Pediatrics; Pathology; Biostatistics; Medical Genetics and Genomics; Surgery; Neuroscience and Pharmacology
- Record Identifier
- 9984656660302771
Metrics
23 Record Views