Tumor and α‐SMA‐expressing stromal cells in pancreatic neuroendocrine tumors have a distinct RNA profile depending on tumor grade
Alpha‐smooth muscle actin (α‐SMA) expression in the stroma is linked to the presence of cancer‐associated fibroblasts and is known to correlate with worse outcomes in various tumors. In this study, using a GeoMx digital spatial profiling approach, we characterized the gene expression of the tumor an...
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| Format: | Article |
| Language: | English |
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Wiley
2025-03-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.13727 |
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| author | Helvijs Niedra Raitis Peculis Rihards Saksis Ilona Mandrika Sofija Vilisova Jurijs Nazarovs Austra Breiksa Aija Gerina Julie Earl Ignacio Ruz‐Caracuel Marta Gabriela Rosas Aldis Pukitis Natalja Senterjakova Vita Rovite |
| author_facet | Helvijs Niedra Raitis Peculis Rihards Saksis Ilona Mandrika Sofija Vilisova Jurijs Nazarovs Austra Breiksa Aija Gerina Julie Earl Ignacio Ruz‐Caracuel Marta Gabriela Rosas Aldis Pukitis Natalja Senterjakova Vita Rovite |
| author_sort | Helvijs Niedra |
| collection | DOAJ |
| description | Alpha‐smooth muscle actin (α‐SMA) expression in the stroma is linked to the presence of cancer‐associated fibroblasts and is known to correlate with worse outcomes in various tumors. In this study, using a GeoMx digital spatial profiling approach, we characterized the gene expression of the tumor and α‐SMA‐expressing stromal cell compartments in pancreatic neuroendocrine tumors (PanNETs). The profiling was performed on tissues from eight retrospective cases (three grade 1, four grade 2, and one grade 3). Selected regions of interest were segmented geometrically based on tissue morphology and fluorescent signals from synaptophysin and α‐SMA markers. The α‐SMA‐expressing stromal‐cell‐associated genes were involved in pathways of extracellular matrix modification, whereas, in tumor cells, the gene expression profiles were associated with pathways involved in cell proliferation. The comparison of gene expression profiles across all three PanNET grades revealed that the differences between grades are not only present at the level of the tumor but also in the α‐SMA‐expressing stromal cells. Furthermore, the tumor cells from regions with a rich presence of adjacent α‐SMA‐expressing stromal cells revealed an upregulation of matrix metalloproteinase‐9 (MMP9) expression in grade 3 tumors. This study provides an in‐depth characterization of gene expression profiles in α‐SMA‐expressing stromal and tumor cells, and outlines potential crosstalk mechanisms. |
| format | Article |
| id | doaj-art-4222e7d8d8b24ddd8653b7177810c4da |
| institution | DOAJ |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-4222e7d8d8b24ddd8653b7177810c4da2025-08-20T03:06:08ZengWileyMolecular Oncology1574-78911878-02612025-03-0119365968110.1002/1878-0261.13727Tumor and α‐SMA‐expressing stromal cells in pancreatic neuroendocrine tumors have a distinct RNA profile depending on tumor gradeHelvijs Niedra0Raitis Peculis1Rihards Saksis2Ilona Mandrika3Sofija Vilisova4Jurijs Nazarovs5Austra Breiksa6Aija Gerina7Julie Earl8Ignacio Ruz‐Caracuel9Marta Gabriela Rosas10Aldis Pukitis11Natalja Senterjakova12Vita Rovite13Department of Molecular and Functional Genomics Latvian Biomedical Research and Study Centre Riga LatviaDepartment of Molecular and Functional Genomics Latvian Biomedical Research and Study Centre Riga LatviaDepartment of Molecular and Functional Genomics Latvian Biomedical Research and Study Centre Riga LatviaDepartment of Molecular and Functional Genomics Latvian Biomedical Research and Study Centre Riga LatviaOncology clinic Pauls Stradins Clinical University Hospital Riga LatviaInstitute of Pathology Pauls Stradins Clinical University Hospital Riga LatviaInstitute of Pathology Pauls Stradins Clinical University Hospital Riga LatviaOncology clinic Pauls Stradins Clinical University Hospital Riga LatviaRamón y Cajal Health Research Institute (IRYCIS) Ramón y Cajal University Hospital. Ctra. Colmenar Viejo, CIBERONC Madrid SpainRamón y Cajal Health Research Institute (IRYCIS) Ramón y Cajal University Hospital. Ctra. Colmenar Viejo, CIBERONC Madrid SpainDepartment of Pathology Ramón y Cajal University Hospital. Ctra Colmenar Viejo Madrid SpainCentre of Gastroenterology, Hepatology and Nutrition Therapy Pauls Stradins Clinical University Hospital Riga LatviaCentre of Gastroenterology, Hepatology and Nutrition Therapy Pauls Stradins Clinical University Hospital Riga LatviaDepartment of Molecular and Functional Genomics Latvian Biomedical Research and Study Centre Riga LatviaAlpha‐smooth muscle actin (α‐SMA) expression in the stroma is linked to the presence of cancer‐associated fibroblasts and is known to correlate with worse outcomes in various tumors. In this study, using a GeoMx digital spatial profiling approach, we characterized the gene expression of the tumor and α‐SMA‐expressing stromal cell compartments in pancreatic neuroendocrine tumors (PanNETs). The profiling was performed on tissues from eight retrospective cases (three grade 1, four grade 2, and one grade 3). Selected regions of interest were segmented geometrically based on tissue morphology and fluorescent signals from synaptophysin and α‐SMA markers. The α‐SMA‐expressing stromal‐cell‐associated genes were involved in pathways of extracellular matrix modification, whereas, in tumor cells, the gene expression profiles were associated with pathways involved in cell proliferation. The comparison of gene expression profiles across all three PanNET grades revealed that the differences between grades are not only present at the level of the tumor but also in the α‐SMA‐expressing stromal cells. Furthermore, the tumor cells from regions with a rich presence of adjacent α‐SMA‐expressing stromal cells revealed an upregulation of matrix metalloproteinase‐9 (MMP9) expression in grade 3 tumors. This study provides an in‐depth characterization of gene expression profiles in α‐SMA‐expressing stromal and tumor cells, and outlines potential crosstalk mechanisms.https://doi.org/10.1002/1878-0261.13727digital spatial profilinggene expressionPancreatic neuroendocrine tumorspathway enrichment analysistumor stroma |
| spellingShingle | Helvijs Niedra Raitis Peculis Rihards Saksis Ilona Mandrika Sofija Vilisova Jurijs Nazarovs Austra Breiksa Aija Gerina Julie Earl Ignacio Ruz‐Caracuel Marta Gabriela Rosas Aldis Pukitis Natalja Senterjakova Vita Rovite Tumor and α‐SMA‐expressing stromal cells in pancreatic neuroendocrine tumors have a distinct RNA profile depending on tumor grade Molecular Oncology digital spatial profiling gene expression Pancreatic neuroendocrine tumors pathway enrichment analysis tumor stroma |
| title | Tumor and α‐SMA‐expressing stromal cells in pancreatic neuroendocrine tumors have a distinct RNA profile depending on tumor grade |
| title_full | Tumor and α‐SMA‐expressing stromal cells in pancreatic neuroendocrine tumors have a distinct RNA profile depending on tumor grade |
| title_fullStr | Tumor and α‐SMA‐expressing stromal cells in pancreatic neuroendocrine tumors have a distinct RNA profile depending on tumor grade |
| title_full_unstemmed | Tumor and α‐SMA‐expressing stromal cells in pancreatic neuroendocrine tumors have a distinct RNA profile depending on tumor grade |
| title_short | Tumor and α‐SMA‐expressing stromal cells in pancreatic neuroendocrine tumors have a distinct RNA profile depending on tumor grade |
| title_sort | tumor and α sma expressing stromal cells in pancreatic neuroendocrine tumors have a distinct rna profile depending on tumor grade |
| topic | digital spatial profiling gene expression Pancreatic neuroendocrine tumors pathway enrichment analysis tumor stroma |
| url | https://doi.org/10.1002/1878-0261.13727 |
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