小肠神经内分泌肿瘤患者的肠系膜纤维化与α-平滑肌肌动蛋白阳性纤维化和COMP表达基质细胞的富集有关。

IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Sebastian D. Graf, Corinna U. Keber, Akira Hattesohl, Julia Teply-Szymanski, Sophia Hattesohl, Marc Guder, Norman Gercke, Pietro Di Fazio, Emily P. Slater, Moritz Jesinghaus, Carsten Denkert, Detlef K. Bartsch, Bettina Lehman
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引用次数: 0

摘要

小肠神经内分泌肿瘤(SI-NETs)经常会发生淋巴结转移(LNM)引起的肠系膜纤维化(MF)。肠系膜纤维化可导致肠梗阻和缺血,使手术切除在技术上具有挑战性。肠系膜纤维化的潜在病理机制仍不甚明了。我们研究了 24 例 SI-NET 患者的肠系膜 LNM 和周围基质区,其中 11 例原位表现为强 MF(MF+),13 例无 MF(MF-)。使用 HTG EdgeSeq 肿瘤生物标记物面板对 LNM 和配对基质样本中的 MF+ 和 MF- 分别进行了差异基因表达评估。通过反转录-定量聚合酶链反应(RT-qPCR)验证了大多数有趣的差异表达基因,同时利用免疫组化(IHC)染色法验证了 MF+ 和 MF- 福尔马林固定、石蜡包埋(FFPE)患者样本的相关蛋白水平。总体而言,与 MF- 相比,用 2549 个基因表达面板测定的 14 个基因在 MF+ 患者中表达不同。其中,9个基因在LNM中表达不同,5个基因在基质组织中表达不同(变化>2倍,P<0.05)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Mesenteric fibrosis in patients with small intestinal neuroendocrine tumors is associated with enrichment of alpha-smooth muscle actin-positive fibrosis and COMP-expressing stromal cells

Mesenteric fibrosis in patients with small intestinal neuroendocrine tumors is associated with enrichment of alpha-smooth muscle actin-positive fibrosis and COMP-expressing stromal cells

Mesenteric fibrosis in patients with small intestinal neuroendocrine tumors is associated with enrichment of alpha-smooth muscle actin-positive fibrosis and COMP-expressing stromal cells

Neuroendocrine tumors of the small intestine (SI-NETs) often develop lymph node metastasis (LNM)-induced 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-NET patients, including 11 with in situ presentation of strong MF (MF+) and 13 without MF (MF−). Differential gene expression was assessed with the HTG EdgeSeq Oncology Biomarker Panel comparing MF+ with MF− within LNM and paired stromal samples, respectively. Most interesting differentially expressed genes were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in combination with validation of associated protein levels utilizing immunohistochemistry (IHC) staining of MF+ and MF– formalin-fixed, paraffin-embedded (FFPE) patient samples. Overall, 14 genes measured with a 2549-gene expression panel were differentially expressed in MF+ patients compared to MF−. Of those, nine were differentially expressed genes in LNM and five genes in the stromal tissue (>2-fold change, p < .05). The top hits included increased COMP and COL11A1 expression in the stroma of MF+ patients compared to MF−, as well as decreased HMGA2, COL6A6, and SLC22A3 expression in LNM of MF+ patients compared to LNM of MF− patients. RT-qPCR confirmed high levels of COMP and COL11A1 in stroma samples of MF+ compared to MF− patients. IHC staining confirmed the enrichment of α-smooth muscle actin-positive fibrosis in MF+ compared to MF− patients with corresponding increase of COMP-expressing stromal cells in MF+. Since COMP is associated with the known driver for fibrosis development transforming growth factor beta and with a cancer-associated fibroblasts enriched environment, it seems to be a promising new target for MF research.

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来源期刊
Journal of Neuroendocrinology
Journal of Neuroendocrinology 医学-内分泌学与代谢
CiteScore
6.40
自引率
6.20%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Journal of Neuroendocrinology provides the principal international focus for the newest ideas in classical neuroendocrinology and its expanding interface with the regulation of behavioural, cognitive, developmental, degenerative and metabolic processes. Through the rapid publication of original manuscripts and provocative review articles, it provides essential reading for basic scientists and clinicians researching in this rapidly expanding field. In determining content, the primary considerations are excellence, relevance and novelty. While Journal of Neuroendocrinology reflects the broad scientific and clinical interests of the BSN membership, the editorial team, led by Professor Julian Mercer, ensures that the journal’s ethos, authorship, content and purpose are those expected of a leading international publication.
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