{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:34:55Z","timestamp":1791981295610,"version":"4.4.0"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,1,21]],"date-time":"2024-01-21T00:00:00Z","timestamp":1705795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Neuroendocrine tumors of the small intestine (SI\u2010NETs) often develop lymph node metastasis (LNM)\u2010induced mesenteric fibrosis (MF). MF can cause intestinal obstruction as well as ischemia and render surgical resection technically challenging. The underlying pathomechanisms of MF are still not well understood. We examined mesenteric LNM and the surrounding stroma compartment from 24 SI\u2010NET patients, including 11 with in situ presentation of strong MF (MF+) and 13 without MF (MF\u2212). Differential gene expression was assessed with the HTG EdgeSeq Oncology Biomarker Panel comparing MF+ with MF\u2212 within LNM and paired stromal samples, respectively. Most interesting differentially expressed genes were validated by reverse transcription\u2010quantitative polymerase chain reaction (RT\u2010qPCR) in combination with validation of associated protein levels utilizing immunohistochemistry (IHC) staining of MF+ and MF\u2013 formalin\u2010fixed, paraffin\u2010embedded (FFPE) patient samples. Overall, 14 genes measured with a 2549\u2010gene expression panel were differentially expressed in MF+ patients compared to MF\u2212. Of those, nine were differentially expressed genes in LNM and five genes in the stromal tissue (&gt;2\u2010fold change,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.05). The top hits included increased\n                    <jats:italic>COMP<\/jats:italic>\n                    and\n                    <jats:italic>COL11A1<\/jats:italic>\n                    expression in the stroma of MF+ patients compared to MF\u2212, as well as decreased\n                    <jats:italic>HMGA2<\/jats:italic>\n                    ,\n                    <jats:italic>COL6A6<\/jats:italic>\n                    , and\n                    <jats:italic>SLC22A3<\/jats:italic>\n                    expression in LNM of MF+ patients compared to LNM of MF\u2212 patients. RT\u2010qPCR confirmed high levels of\n                    <jats:italic>COMP<\/jats:italic>\n                    and\n                    <jats:italic>COL11A1<\/jats:italic>\n                    in stroma samples of MF+ compared to MF\u2212 patients. IHC staining confirmed the enrichment of \u03b1\u2010smooth muscle actin\u2010positive fibrosis in MF+ compared to MF\u2212 patients with corresponding increase of COMP\u2010expressing stromal cells in MF+. Since COMP is associated with the known driver for fibrosis development transforming growth factor beta and with a cancer\u2010associated fibroblasts enriched environment, it seems to be a promising new target for MF research.\n                  <\/jats:p>","DOI":"10.1111\/jne.13364","type":"journal-article","created":{"date-parts":[[2024,1,21]],"date-time":"2024-01-21T19:34:36Z","timestamp":1705865676000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Mesenteric fibrosis in patients with small intestinal neuroendocrine tumors is associated with enrichment of alpha\u2010smooth muscle actin\u2010positive fibrosis and\n                    <scp>COMP<\/scp>\n                    \u2010expressing stromal cells"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4713-7026","authenticated-orcid":false,"given":"Sebastian 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Surgery Philipps\u2010University Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily P.","family":"Slater","sequence":"additional","affiliation":[{"name":"Department of Visceral, Thoracic and Vascular Surgery Philipps\u2010University Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Jesinghaus","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Marburg Philipps\u2010University Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Denkert","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Marburg Philipps\u2010University Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlef K.","family":"Bartsch","sequence":"additional","affiliation":[{"name":"Department of Visceral, Thoracic and Vascular Surgery 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