Gene Expression Profiling of Pancreas Neuroendocrine Tumors with Different Ki67-Based Grades
Pancreatic neuroendocrine tumors (PanNETs) display variable aggressive behavior. A major predictor of survival is tumor grade based on the Ki67 proliferation index. As information on transcriptomic profiles of PanNETs with different tumor grades is limited, we investigated 29 PanNETs (17 G1, 7 G2, 5...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/9/2054 |
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| author | Michele Simbolo Mirna Bilotta Andrea Mafficini Claudio Luchini Daniela Furlan Frediano Inzani Gianluigi Petrone Davide Bonvissuto Stefano La Rosa Giovanni Schinzari Antonio Bianchi Ernesto Rossi Roberta Menghi Felice Giuliante Stefania Boccia Aldo Scarpa Guido Rindi |
| author_facet | Michele Simbolo Mirna Bilotta Andrea Mafficini Claudio Luchini Daniela Furlan Frediano Inzani Gianluigi Petrone Davide Bonvissuto Stefano La Rosa Giovanni Schinzari Antonio Bianchi Ernesto Rossi Roberta Menghi Felice Giuliante Stefania Boccia Aldo Scarpa Guido Rindi |
| author_sort | Michele Simbolo |
| collection | DOAJ |
| description | Pancreatic neuroendocrine tumors (PanNETs) display variable aggressive behavior. A major predictor of survival is tumor grade based on the Ki67 proliferation index. As information on transcriptomic profiles of PanNETs with different tumor grades is limited, we investigated 29 PanNETs (17 G1, 7 G2, 5 G3) for their expression profiles, mutations in 16 PanNET relevant genes and LINE-1 DNA methylation profiles. A total of 3050 genes were differentially expressed between tumors with different grades (<i>p</i> < 0.05): 1279 in G3 vs. G2; 2757 in G3 vs. G1; and 203 in G2 vs. G1. Mutational analysis showed 57 alterations in 11 genes, the most frequent being <i>MEN1</i> (18/29), <i>DAXX</i> (7/29), <i>ATRX</i> (6/29) and <i>MUTYH</i> (5/29). The presence and type of mutations did not correlate with the specific expression profiles associated with different grades. LINE-1 showed significantly lower methylation in G2/G3 versus G1 tumors (<i>p</i> = 0.007). The expression profiles of matched primaries and metastasis (nodal, hepatic and colorectal wall) of three cases confirmed the role of Ki67 in defining specific expression profiles, which clustered according to tumor grades, independently from anatomic location or patient of origin. Such data call for future exploration of the role of Ki67 in tumor progression, given its involvement in chromosomal stability. |
| first_indexed | 2024-03-10T12:02:20Z |
| format | Article |
| id | doaj.art-e9937b9671614f79aee9377690853036 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T12:02:20Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-e9937b9671614f79aee93776908530362023-11-21T16:55:27ZengMDPI AGCancers2072-66942021-04-01139205410.3390/cancers13092054Gene Expression Profiling of Pancreas Neuroendocrine Tumors with Different Ki67-Based GradesMichele Simbolo0Mirna Bilotta1Andrea Mafficini2Claudio Luchini3Daniela Furlan4Frediano Inzani5Gianluigi Petrone6Davide Bonvissuto7Stefano La Rosa8Giovanni Schinzari9Antonio Bianchi10Ernesto Rossi11Roberta Menghi12Felice Giuliante13Stefania Boccia14Aldo Scarpa15Guido Rindi16Section of Pathology, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, ItalySection of Anatomic Pathology, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00100 Roma, ItalySection of Pathology, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, ItalySection of Pathology, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, ItalyPathology Unit, Department of Medicine and Surgery, University of Insubria, 21100 Varese, ItalyAnatomic Pathology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00100 Roma, ItalyAnatomic Pathology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00100 Roma, ItalySection of Human Anatomy, Department of Neurosciences, Università Cattolica del Sacro Cuore, 00100 Roma, ItalyPathology Unit, Department of Medicine and Surgery, University of Insubria, 21100 Varese, ItalyENETS Center of Excellence of Roma, 00100 Roma, ItalyAnatomic Pathology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00100 Roma, ItalyDepartment of Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00100 Roma, ItalyAnatomic Pathology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00100 Roma, ItalyAnatomic Pathology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00100 Roma, ItalySection of Hygiene, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00100 Roma, ItalySection of Pathology, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, ItalySection of Anatomic Pathology, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00100 Roma, ItalyPancreatic neuroendocrine tumors (PanNETs) display variable aggressive behavior. A major predictor of survival is tumor grade based on the Ki67 proliferation index. As information on transcriptomic profiles of PanNETs with different tumor grades is limited, we investigated 29 PanNETs (17 G1, 7 G2, 5 G3) for their expression profiles, mutations in 16 PanNET relevant genes and LINE-1 DNA methylation profiles. A total of 3050 genes were differentially expressed between tumors with different grades (<i>p</i> < 0.05): 1279 in G3 vs. G2; 2757 in G3 vs. G1; and 203 in G2 vs. G1. Mutational analysis showed 57 alterations in 11 genes, the most frequent being <i>MEN1</i> (18/29), <i>DAXX</i> (7/29), <i>ATRX</i> (6/29) and <i>MUTYH</i> (5/29). The presence and type of mutations did not correlate with the specific expression profiles associated with different grades. LINE-1 showed significantly lower methylation in G2/G3 versus G1 tumors (<i>p</i> = 0.007). The expression profiles of matched primaries and metastasis (nodal, hepatic and colorectal wall) of three cases confirmed the role of Ki67 in defining specific expression profiles, which clustered according to tumor grades, independently from anatomic location or patient of origin. Such data call for future exploration of the role of Ki67 in tumor progression, given its involvement in chromosomal stability.https://www.mdpi.com/2072-6694/13/9/2054pancreasneuroendocrine tumorNETKi67gradeLINE-1 |
| spellingShingle | Michele Simbolo Mirna Bilotta Andrea Mafficini Claudio Luchini Daniela Furlan Frediano Inzani Gianluigi Petrone Davide Bonvissuto Stefano La Rosa Giovanni Schinzari Antonio Bianchi Ernesto Rossi Roberta Menghi Felice Giuliante Stefania Boccia Aldo Scarpa Guido Rindi Gene Expression Profiling of Pancreas Neuroendocrine Tumors with Different Ki67-Based Grades Cancers pancreas neuroendocrine tumor NET Ki67 grade LINE-1 |
| title | Gene Expression Profiling of Pancreas Neuroendocrine Tumors with Different Ki67-Based Grades |
| title_full | Gene Expression Profiling of Pancreas Neuroendocrine Tumors with Different Ki67-Based Grades |
| title_fullStr | Gene Expression Profiling of Pancreas Neuroendocrine Tumors with Different Ki67-Based Grades |
| title_full_unstemmed | Gene Expression Profiling of Pancreas Neuroendocrine Tumors with Different Ki67-Based Grades |
| title_short | Gene Expression Profiling of Pancreas Neuroendocrine Tumors with Different Ki67-Based Grades |
| title_sort | gene expression profiling of pancreas neuroendocrine tumors with different ki67 based grades |
| topic | pancreas neuroendocrine tumor NET Ki67 grade LINE-1 |
| url | https://www.mdpi.com/2072-6694/13/9/2054 |
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