Transcriptomic profiling of pancreatic neuroendocrine tumors: dysregulation of WNT, MAPK, PI3K, neddylation pathways and potential non-invasive biomarkers.

The study aimed to identify altered signaling pathways and potential non-invasive biomarkers for pancreatic neuroendocrine tumors (PanNETs) through transcriptomic profiling of tumor tissues. The analysis encompassed samples from non-functional PanNETs (NF-PanNETs), insulinomas, and tumor-adjacent pa...

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Main Authors: Helvijs Niedra, Olesja Rogoza, Rihards Saksis, Raitis Peculis, Anzela Halilova, Aija Gerina, Sofija Vilisova, Natalja Senterjakova, Aldis Pukitis, Ignacio Ruz-Caracuel, Julie Earl, Georgina Kolnikova, Peter Dubovan, Miroslav Tomas, Peter Makovicky, Maria Urbanova, Bozena Smolkova, Eythimios Koniaris, Ioanna Aggelioudaki, Agapi Kataki, Vita Rovite
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0325672
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author Helvijs Niedra
Olesja Rogoza
Rihards Saksis
Raitis Peculis
Anzela Halilova
Aija Gerina
Sofija Vilisova
Natalja Senterjakova
Aldis Pukitis
Ignacio Ruz-Caracuel
Julie Earl
Georgina Kolnikova
Peter Dubovan
Miroslav Tomas
Peter Makovicky
Maria Urbanova
Bozena Smolkova
Eythimios Koniaris
Ioanna Aggelioudaki
Agapi Kataki
Vita Rovite
author_facet Helvijs Niedra
Olesja Rogoza
Rihards Saksis
Raitis Peculis
Anzela Halilova
Aija Gerina
Sofija Vilisova
Natalja Senterjakova
Aldis Pukitis
Ignacio Ruz-Caracuel
Julie Earl
Georgina Kolnikova
Peter Dubovan
Miroslav Tomas
Peter Makovicky
Maria Urbanova
Bozena Smolkova
Eythimios Koniaris
Ioanna Aggelioudaki
Agapi Kataki
Vita Rovite
author_sort Helvijs Niedra
collection DOAJ
description The study aimed to identify altered signaling pathways and potential non-invasive biomarkers for pancreatic neuroendocrine tumors (PanNETs) through transcriptomic profiling of tumor tissues. The analysis encompassed samples from non-functional PanNETs (NF-PanNETs), insulinomas, and tumor-adjacent pancreatic tissues (TAPT). In the differential expression analysis comparing PanNETs and TAPTs, we identified 1,210 differentially expressed genes at a false discovery rate significance threshold of < 0.05 and with Log2FoldChange values of > 0.5 and <-0.5. Further pathway enrichment analysis revealed a multitude of overrepresented signaling pathways related to cell proliferation, survival, and tumorigenesis. Significant findings included the Beta-catenin-independent and TCF-dependent WNT signaling pathways, MAPK1/MAPK3 signaling, and terms associated with PI3K/AKT/mTOR signaling. Among the list of DEGs, we also identified 28 upregulated genes encoding cell surface proteins and 24 upregulated genes encoding cancer-associated secretome proteins. Since the proteins of these genes are found in the bloodstream, there is potential for further testing of these markers as biomarkers for liquid biopsy assays. Overall, these findings underscore the promise of transcriptomic landscape analysis in identifying PanNET-specific non-invasive biomarkers and uncovering potential therapeutic targets.
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spelling doaj-art-abeba8a9a0ef479a82c5229255924d732025-08-20T03:22:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01206e032567210.1371/journal.pone.0325672Transcriptomic profiling of pancreatic neuroendocrine tumors: dysregulation of WNT, MAPK, PI3K, neddylation pathways and potential non-invasive biomarkers.Helvijs NiedraOlesja RogozaRihards SaksisRaitis PeculisAnzela HalilovaAija GerinaSofija VilisovaNatalja SenterjakovaAldis PukitisIgnacio Ruz-CaracuelJulie EarlGeorgina KolnikovaPeter DubovanMiroslav TomasPeter MakovickyMaria UrbanovaBozena SmolkovaEythimios KoniarisIoanna AggelioudakiAgapi KatakiVita RoviteThe study aimed to identify altered signaling pathways and potential non-invasive biomarkers for pancreatic neuroendocrine tumors (PanNETs) through transcriptomic profiling of tumor tissues. The analysis encompassed samples from non-functional PanNETs (NF-PanNETs), insulinomas, and tumor-adjacent pancreatic tissues (TAPT). In the differential expression analysis comparing PanNETs and TAPTs, we identified 1,210 differentially expressed genes at a false discovery rate significance threshold of < 0.05 and with Log2FoldChange values of > 0.5 and <-0.5. Further pathway enrichment analysis revealed a multitude of overrepresented signaling pathways related to cell proliferation, survival, and tumorigenesis. Significant findings included the Beta-catenin-independent and TCF-dependent WNT signaling pathways, MAPK1/MAPK3 signaling, and terms associated with PI3K/AKT/mTOR signaling. Among the list of DEGs, we also identified 28 upregulated genes encoding cell surface proteins and 24 upregulated genes encoding cancer-associated secretome proteins. Since the proteins of these genes are found in the bloodstream, there is potential for further testing of these markers as biomarkers for liquid biopsy assays. Overall, these findings underscore the promise of transcriptomic landscape analysis in identifying PanNET-specific non-invasive biomarkers and uncovering potential therapeutic targets.https://doi.org/10.1371/journal.pone.0325672
spellingShingle Helvijs Niedra
Olesja Rogoza
Rihards Saksis
Raitis Peculis
Anzela Halilova
Aija Gerina
Sofija Vilisova
Natalja Senterjakova
Aldis Pukitis
Ignacio Ruz-Caracuel
Julie Earl
Georgina Kolnikova
Peter Dubovan
Miroslav Tomas
Peter Makovicky
Maria Urbanova
Bozena Smolkova
Eythimios Koniaris
Ioanna Aggelioudaki
Agapi Kataki
Vita Rovite
Transcriptomic profiling of pancreatic neuroendocrine tumors: dysregulation of WNT, MAPK, PI3K, neddylation pathways and potential non-invasive biomarkers.
PLoS ONE
title Transcriptomic profiling of pancreatic neuroendocrine tumors: dysregulation of WNT, MAPK, PI3K, neddylation pathways and potential non-invasive biomarkers.
title_full Transcriptomic profiling of pancreatic neuroendocrine tumors: dysregulation of WNT, MAPK, PI3K, neddylation pathways and potential non-invasive biomarkers.
title_fullStr Transcriptomic profiling of pancreatic neuroendocrine tumors: dysregulation of WNT, MAPK, PI3K, neddylation pathways and potential non-invasive biomarkers.
title_full_unstemmed Transcriptomic profiling of pancreatic neuroendocrine tumors: dysregulation of WNT, MAPK, PI3K, neddylation pathways and potential non-invasive biomarkers.
title_short Transcriptomic profiling of pancreatic neuroendocrine tumors: dysregulation of WNT, MAPK, PI3K, neddylation pathways and potential non-invasive biomarkers.
title_sort transcriptomic profiling of pancreatic neuroendocrine tumors dysregulation of wnt mapk pi3k neddylation pathways and potential non invasive biomarkers
url https://doi.org/10.1371/journal.pone.0325672
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