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 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.
Authors
- Olesja Rogoza
- Agapi Kataki (ORCID: https://orcid.org/0009-0008-8930-5383)
- Peter J. Makovicky (ORCID: https://orcid.org/0000-0001-9307-9982)
- Rihards Saksis (ORCID: https://orcid.org/0009-0002-5017-5688)
- Maria Urbanova (ORCID: https://orcid.org/0000-0003-0931-0032)
- Raitis Pečulis (ORCID: https://orcid.org/0000-0003-1107-4550)
- Efthymios Koniaris (ORCID: https://orcid.org/0009-0005-7804-1472)
- Georgina Kolníková
- Peter Dubovan (ORCID: https://orcid.org/0000-0002-0853-4045)
- Aldis Puķītis (ORCID: https://orcid.org/0000-0003-1566-4996)
- Helvijs Niedra (ORCID: https://orcid.org/0000-0003-4396-4021)
- Julie Earl (ORCID: https://orcid.org/0000-0001-9360-4716)
- Vita Rovīte (ORCID: https://orcid.org/0000-0001-9368-5210)
- Božena Smolková (ORCID: https://orcid.org/0000-0002-4906-5652)
- Ignacio Ruz‐Caracuel (ORCID: https://orcid.org/0000-0002-2298-4683)
- Miroslav Tomáš (ORCID: https://orcid.org/0000-0002-1114-5120)
- Sofija Vilisova
- Natalja Senterjakova
- Aija Gerina
- Ioanna Aggelioudaki
- Anzela Halilova
Institutions
- Latvian Biomedical Research and Study Centre (LV)
- Institute of Chemistry of the Slovak Academy of Sciences (SK)
- Slovak Medical University (SK)
- Instituto Cajal (ES)
- National Institute of Cardiovascular Diseases (SK)
- Pauls Stradiņš Clinical University Hospital (LV)
- Aretaeio Hospital (GR)
- Biomedical Research Center of the Slovak Academy of Sciences (SK)
- Hospital Universitario Ramón y Cajal (ES)
- Hippocration General Hospital (GR)
Publication Details
- Journal
- PLoS ONE
- Published
- 2025-06-16
- DOI
- https://doi.org/10.1371/journal.pone.0325672
- Primary Topic
- Neuroendocrine Tumor Research Advances
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Slovenská Akadémia Vied
- Horizon 2020 Framework Programme
- European Regional Development Fund
- European Social Fund