James Saller1, Shabnam Seydafkan1, Mohammad Shahid1, Manoj Gadara1, Mauro Cives2, Steven A Eschrich3, David Boulware3, Jonathan R Strosberg2, Nasir Aejaz4, Domenico Coppola5,6,7,8. 1. Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. 2. Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. 3. Department of Bioinformatics and Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. 4. Diagnostic and Experimental Pathology, Eli Lilly and Company, Indianapolis, IN, U.S.A. 5. Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. domenico.coppola@fdhs.com. 6. Department of Chemical Biology and Molecular Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. 7. Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. 8. Department of Oncological Sciences, University of South Florida, Tampa, FL, U.S.A.
Abstract
BACKGROUND/AIM: Low-grade pancreatic neuroendocrine tumors (LG-PNETs) behave unpredictably. The aim of the study was to identify biomarkers that predict PNET metastasis to improve treatment selection. PATIENTS AND METHODS: Five patients with primary non-metastatic LG-PNETs, six with primary LG-PNETs with synchronous or metachronous metastases (M-PNETs), and six metastatic to liver LG-PNETs (ML-PNETs) from the group of six M-PNET patients were selected. RNA data were normalized using iterative rank-order normalization. Student's t-test identified differentially-expressed genes in LG-PNETs versus M-PNETs. A 2-fold difference in expression was considered to be significant. Results were validated with an independent dataset of LG-PNETs and metastatic LG-PNETs. RESULTS: Overall, 195 genes had a >2-fold change (in either direction). A total of 29 genes were differentially overexpressed in M-PNETs. Erythrocyte membrane protein band 4.1-like 5 (EPB41L5) had a 2.07-fold change increase in M-PNETs and the smallest p-value. EPB41L5 was not statistically different between M-PNETs and ML-PNETs. EPB41L5 differential expression between primary and metastatic LG-PNETs was confirmed by immunohistochemistry. CONCLUSION: These results support further investigation into whether EPB41L5 is a biomarker of PNETs with high risk for metastases. Copyright
BACKGROUND/AIM: Low-grade pancreatic neuroendocrine tumors (LG-PNETs) behave unpredictably. The aim of the study was to identify biomarkers that predict PNET metastasis to improve treatment selection. PATIENTS AND METHODS: Five patients with primary non-metastatic LG-PNETs, six with primary LG-PNETs with synchronous or metachronous metastases (M-PNETs), and six metastatic to liver LG-PNETs (ML-PNETs) from the group of six M-PNET patients were selected. RNA data were normalized using iterative rank-order normalization. Student's t-test identified differentially-expressed genes in LG-PNETs versus M-PNETs. A 2-fold difference in expression was considered to be significant. Results were validated with an independent dataset of LG-PNETs and metastatic LG-PNETs. RESULTS: Overall, 195 genes had a >2-fold change (in either direction). A total of 29 genes were differentially overexpressed in M-PNETs. Erythrocyte membrane protein band 4.1-like 5 (EPB41L5) had a 2.07-fold change increase in M-PNETs and the smallest p-value. EPB41L5 was not statistically different between M-PNETs and ML-PNETs. EPB41L5 differential expression between primary and metastatic LG-PNETs was confirmed by immunohistochemistry. CONCLUSION: These results support further investigation into whether EPB41L5 is a biomarker of PNETs with high risk for metastases. Copyright
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