Impact of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) single nucleotide polymorphisms on outcome in gastroenteropancreatic neuroendocrine neoplasms
Angiogenesis represents a key event in cancer development, leading to local invasion e metastatization, and might be considered a basic feature in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with a high expression of angiogenic molecules. We aimed to analyze the prognostic and predict...
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| Veröffentlicht in: | PloS one 2018-05, Vol.13 (5), p.e0197035-e0197035 |
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| creator | Berardi, Rossana Torniai, Mariangela Partelli, Stefano Rubini, Corrado Pagliaretta, Silvia Savini, Agnese Polenta, Vanessa Santoni, Matteo Giampieri, Riccardo Onorati, Sofia Barucca, Federica Murrone, Alberto Bianchi, Francesca Falconi, Massimo |
| description | Angiogenesis represents a key event in cancer development, leading to local invasion e metastatization, and might be considered a basic feature in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with a high expression of angiogenic molecules. We aimed to analyze the prognostic and predictive role of angiogenic factors in GEP-NENs through the analysis of single nucleotide polymorphisms (SNPs) of VEGF-A, VEGFR2 and VEGFR3. The genomic DNA of 58 consecutive patients with GEP-NENs treated at our Institution was extracted from peripheral blood. Two SNPs were identified respectively in VEGF-A (rs2010963G>C, rs699947A>C), VEGFR-2 (rs2305948C>T, rs1870377T>A), and VEGFR-3 (rs307821T>C, rs307826C>A) gene. Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. Median age was 57 years (range 24-79 years); 32 patients were male and 77.5% of NENs were localized in the pancreas. The allele frequency of VEGFR-2 rs2305948T and of VEGF-A rs2010963C showed a trend of higher frequency than in general population (12.1% vs. 8.0% and 34.5% vs. 31.2%, respectively). Three out SNPs (VEGF-A rs699947C, VEGF-A rs2010963GC and VEGFR-3 rs307821C) showed a correlation with an increased risk of disease relapse. Moreover median PFS changes according to the presence of 0-1 SNPs (20.7% of cases; 61.9 months), 2 SNPs (25.9%; 49.2 months) and 3 SNPs (53.4%; 27.8 months) (p = 0.034). Results suggest, for the first time, that specific SNPs in VEGF-A and VEGFR-3 correlate with poor prognosis in GEP-NENs. The identification of this new prognostic factor might be helpful in order to optimize the management of these heterogeneous neoplasms. |
| doi_str_mv | 10.1371/journal.pone.0197035 |
| format | Article |
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We aimed to analyze the prognostic and predictive role of angiogenic factors in GEP-NENs through the analysis of single nucleotide polymorphisms (SNPs) of VEGF-A, VEGFR2 and VEGFR3. The genomic DNA of 58 consecutive patients with GEP-NENs treated at our Institution was extracted from peripheral blood. Two SNPs were identified respectively in VEGF-A (rs2010963G>C, rs699947A>C), VEGFR-2 (rs2305948C>T, rs1870377T>A), and VEGFR-3 (rs307821T>C, rs307826C>A) gene. Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. Median age was 57 years (range 24-79 years); 32 patients were male and 77.5% of NENs were localized in the pancreas. The allele frequency of VEGFR-2 rs2305948T and of VEGF-A rs2010963C showed a trend of higher frequency than in general population (12.1% vs. 8.0% and 34.5% vs. 31.2%, respectively). Three out SNPs (VEGF-A rs699947C, VEGF-A rs2010963GC and VEGFR-3 rs307821C) showed a correlation with an increased risk of disease relapse. Moreover median PFS changes according to the presence of 0-1 SNPs (20.7% of cases; 61.9 months), 2 SNPs (25.9%; 49.2 months) and 3 SNPs (53.4%; 27.8 months) (p = 0.034). Results suggest, for the first time, that specific SNPs in VEGF-A and VEGFR-3 correlate with poor prognosis in GEP-NENs. The identification of this new prognostic factor might be helpful in order to optimize the management of these heterogeneous neoplasms.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0197035</identifier><identifier>PMID: 29787601</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Angiogenesis ; Biology and Life Sciences ; Cancer ; Cancer therapies ; Colorectal cancer ; Deoxyribonucleic acid ; DNA ; Female ; Gene Expression Regulation, Neoplastic ; Gene frequency ; Health risks ; Histopathology ; Humans ; Hypoxia ; Intestinal Neoplasms - genetics ; Intestinal Neoplasms - mortality ; Intestinal Neoplasms - pathology ; Male ; Medical diagnosis ; Medicine and Health Sciences ; Metastasis ; Middle Aged ; Molecular chains ; Neoplasia ; Neoplasm Recurrence, Local - genetics ; Neoplasm Recurrence, Local - mortality ; Neoplasm Recurrence, Local - pathology ; Neoplasms ; Neuroendocrine tumors ; Neuroendocrine Tumors - genetics ; Neuroendocrine Tumors - mortality ; Neuroendocrine Tumors - pathology ; Neurosciences ; Pancreas ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - mortality ; Pancreatic Neoplasms - pathology ; Patients ; Peripheral blood ; Polymorphism, Single Nucleotide ; Population ; Prognosis ; Risk assessment ; Signal transduction ; Single-nucleotide polymorphism ; Stomach Neoplasms - genetics ; Stomach Neoplasms - mortality ; Stomach Neoplasms - pathology ; Survival Rate ; Tumors ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor Receptor-2 - genetics ; Vascular Endothelial Growth Factor Receptor-3 - genetics ; Vascular endothelial growth factor receptors ; Young Adult</subject><ispartof>PloS one, 2018-05, Vol.13 (5), p.e0197035-e0197035</ispartof><rights>2018 Berardi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Berardi et al 2018 Berardi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-18cb7716a4212460fab91aff0b792aea3101ec41ac33aafdf451cab772099393</citedby><cites>FETCH-LOGICAL-c526t-18cb7716a4212460fab91aff0b792aea3101ec41ac33aafdf451cab772099393</cites><orcidid>0000-0002-9529-2960</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963762/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963762/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29787601$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Berardi, Rossana</creatorcontrib><creatorcontrib>Torniai, Mariangela</creatorcontrib><creatorcontrib>Partelli, Stefano</creatorcontrib><creatorcontrib>Rubini, Corrado</creatorcontrib><creatorcontrib>Pagliaretta, Silvia</creatorcontrib><creatorcontrib>Savini, Agnese</creatorcontrib><creatorcontrib>Polenta, Vanessa</creatorcontrib><creatorcontrib>Santoni, Matteo</creatorcontrib><creatorcontrib>Giampieri, Riccardo</creatorcontrib><creatorcontrib>Onorati, Sofia</creatorcontrib><creatorcontrib>Barucca, Federica</creatorcontrib><creatorcontrib>Murrone, Alberto</creatorcontrib><creatorcontrib>Bianchi, Francesca</creatorcontrib><creatorcontrib>Falconi, Massimo</creatorcontrib><title>Impact of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) single nucleotide polymorphisms on outcome in gastroenteropancreatic neuroendocrine neoplasms</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Angiogenesis represents a key event in cancer development, leading to local invasion e metastatization, and might be considered a basic feature in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with a high expression of angiogenic molecules. We aimed to analyze the prognostic and predictive role of angiogenic factors in GEP-NENs through the analysis of single nucleotide polymorphisms (SNPs) of VEGF-A, VEGFR2 and VEGFR3. The genomic DNA of 58 consecutive patients with GEP-NENs treated at our Institution was extracted from peripheral blood. Two SNPs were identified respectively in VEGF-A (rs2010963G>C, rs699947A>C), VEGFR-2 (rs2305948C>T, rs1870377T>A), and VEGFR-3 (rs307821T>C, rs307826C>A) gene. Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. Median age was 57 years (range 24-79 years); 32 patients were male and 77.5% of NENs were localized in the pancreas. The allele frequency of VEGFR-2 rs2305948T and of VEGF-A rs2010963C showed a trend of higher frequency than in general population (12.1% vs. 8.0% and 34.5% vs. 31.2%, respectively). Three out SNPs (VEGF-A rs699947C, VEGF-A rs2010963GC and VEGFR-3 rs307821C) showed a correlation with an increased risk of disease relapse. Moreover median PFS changes according to the presence of 0-1 SNPs (20.7% of cases; 61.9 months), 2 SNPs (25.9%; 49.2 months) and 3 SNPs (53.4%; 27.8 months) (p = 0.034). Results suggest, for the first time, that specific SNPs in VEGF-A and VEGFR-3 correlate with poor prognosis in GEP-NENs. The identification of this new prognostic factor might be helpful in order to optimize the management of these heterogeneous neoplasms.</description><subject>Adult</subject><subject>Aged</subject><subject>Angiogenesis</subject><subject>Biology and Life Sciences</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Colorectal cancer</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene frequency</subject><subject>Health risks</subject><subject>Histopathology</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Intestinal Neoplasms - genetics</subject><subject>Intestinal Neoplasms - mortality</subject><subject>Intestinal Neoplasms - pathology</subject><subject>Male</subject><subject>Medical diagnosis</subject><subject>Medicine and Health Sciences</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Molecular chains</subject><subject>Neoplasia</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>Neoplasm Recurrence, Local - mortality</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Neoplasms</subject><subject>Neuroendocrine tumors</subject><subject>Neuroendocrine Tumors - genetics</subject><subject>Neuroendocrine Tumors - mortality</subject><subject>Neuroendocrine Tumors - pathology</subject><subject>Neurosciences</subject><subject>Pancreas</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - mortality</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Patients</subject><subject>Peripheral blood</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population</subject><subject>Prognosis</subject><subject>Risk assessment</subject><subject>Signal transduction</subject><subject>Single-nucleotide polymorphism</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - mortality</subject><subject>Stomach Neoplasms - pathology</subject><subject>Survival Rate</subject><subject>Tumors</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - 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genetics</topic><topic>Stomach Neoplasms - mortality</topic><topic>Stomach Neoplasms - pathology</topic><topic>Survival Rate</topic><topic>Tumors</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><topic>Vascular Endothelial Growth Factor Receptor-2 - genetics</topic><topic>Vascular Endothelial Growth Factor Receptor-3 - genetics</topic><topic>Vascular endothelial growth factor receptors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Berardi, Rossana</creatorcontrib><creatorcontrib>Torniai, Mariangela</creatorcontrib><creatorcontrib>Partelli, Stefano</creatorcontrib><creatorcontrib>Rubini, Corrado</creatorcontrib><creatorcontrib>Pagliaretta, Silvia</creatorcontrib><creatorcontrib>Savini, Agnese</creatorcontrib><creatorcontrib>Polenta, Vanessa</creatorcontrib><creatorcontrib>Santoni, Matteo</creatorcontrib><creatorcontrib>Giampieri, Riccardo</creatorcontrib><creatorcontrib>Onorati, Sofia</creatorcontrib><creatorcontrib>Barucca, Federica</creatorcontrib><creatorcontrib>Murrone, Alberto</creatorcontrib><creatorcontrib>Bianchi, Francesca</creatorcontrib><creatorcontrib>Falconi, Massimo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Berardi, Rossana</au><au>Torniai, Mariangela</au><au>Partelli, Stefano</au><au>Rubini, Corrado</au><au>Pagliaretta, Silvia</au><au>Savini, Agnese</au><au>Polenta, Vanessa</au><au>Santoni, Matteo</au><au>Giampieri, Riccardo</au><au>Onorati, Sofia</au><au>Barucca, Federica</au><au>Murrone, Alberto</au><au>Bianchi, Francesca</au><au>Falconi, Massimo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) single nucleotide polymorphisms on outcome in gastroenteropancreatic neuroendocrine neoplasms</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-05-22</date><risdate>2018</risdate><volume>13</volume><issue>5</issue><spage>e0197035</spage><epage>e0197035</epage><pages>e0197035-e0197035</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Angiogenesis represents a key event in cancer development, leading to local invasion e metastatization, and might be considered a basic feature in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with a high expression of angiogenic molecules. We aimed to analyze the prognostic and predictive role of angiogenic factors in GEP-NENs through the analysis of single nucleotide polymorphisms (SNPs) of VEGF-A, VEGFR2 and VEGFR3. The genomic DNA of 58 consecutive patients with GEP-NENs treated at our Institution was extracted from peripheral blood. Two SNPs were identified respectively in VEGF-A (rs2010963G>C, rs699947A>C), VEGFR-2 (rs2305948C>T, rs1870377T>A), and VEGFR-3 (rs307821T>C, rs307826C>A) gene. Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. Median age was 57 years (range 24-79 years); 32 patients were male and 77.5% of NENs were localized in the pancreas. The allele frequency of VEGFR-2 rs2305948T and of VEGF-A rs2010963C showed a trend of higher frequency than in general population (12.1% vs. 8.0% and 34.5% vs. 31.2%, respectively). Three out SNPs (VEGF-A rs699947C, VEGF-A rs2010963GC and VEGFR-3 rs307821C) showed a correlation with an increased risk of disease relapse. Moreover median PFS changes according to the presence of 0-1 SNPs (20.7% of cases; 61.9 months), 2 SNPs (25.9%; 49.2 months) and 3 SNPs (53.4%; 27.8 months) (p = 0.034). Results suggest, for the first time, that specific SNPs in VEGF-A and VEGFR-3 correlate with poor prognosis in GEP-NENs. The identification of this new prognostic factor might be helpful in order to optimize the management of these heterogeneous neoplasms.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29787601</pmid><doi>10.1371/journal.pone.0197035</doi><orcidid>https://orcid.org/0000-0002-9529-2960</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2018-05, Vol.13 (5), p.e0197035-e0197035 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2042728848 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adult Aged Angiogenesis Biology and Life Sciences Cancer Cancer therapies Colorectal cancer Deoxyribonucleic acid DNA Female Gene Expression Regulation, Neoplastic Gene frequency Health risks Histopathology Humans Hypoxia Intestinal Neoplasms - genetics Intestinal Neoplasms - mortality Intestinal Neoplasms - pathology Male Medical diagnosis Medicine and Health Sciences Metastasis Middle Aged Molecular chains Neoplasia Neoplasm Recurrence, Local - genetics Neoplasm Recurrence, Local - mortality Neoplasm Recurrence, Local - pathology Neoplasms Neuroendocrine tumors Neuroendocrine Tumors - genetics Neuroendocrine Tumors - mortality Neuroendocrine Tumors - pathology Neurosciences Pancreas Pancreatic Neoplasms - genetics Pancreatic Neoplasms - mortality Pancreatic Neoplasms - pathology Patients Peripheral blood Polymorphism, Single Nucleotide Population Prognosis Risk assessment Signal transduction Single-nucleotide polymorphism Stomach Neoplasms - genetics Stomach Neoplasms - mortality Stomach Neoplasms - pathology Survival Rate Tumors Vascular endothelial growth factor Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor Receptor-2 - genetics Vascular Endothelial Growth Factor Receptor-3 - genetics Vascular endothelial growth factor receptors Young Adult |
| title | Impact of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) single nucleotide polymorphisms on outcome in gastroenteropancreatic neuroendocrine neoplasms |
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