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TYROBP 作为胆管癌、肾癌和腹主动脉瘤的分子靶点。

TYROBP as a molecular target in cholangiocarcinoma, renal cancer and abdominal aortic aneurysm.

机构信息

Gastrointestinal Rehabilitation Center, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, P. R. China.

Department of Vascular Surgery, Fuxing Hospital Affiliated to Capital Medical University, Beijing, P. R. China.

出版信息

Medicine (Baltimore). 2024 Jan 5;103(1):e36843. doi: 10.1097/MD.0000000000036843.

Abstract

Cholangiocarcinoma occurs when there is a malignant tumor in the bile duct system. Renal cancer originates from renal tubular epithelial cells. Abdominal aortic aneurysm (AAA) is a permanently localized dilation caused by a lesion or injury to abdominal aortic wall. However, the relationship between TYROBP and cholangiocarcinoma, renal cancer and AAA remains unclear. The profiles of cholangiocarcinoma dataset GSE107943, renal cell carcinoma dataset GSE213324, and AAA dataset GSE47472 were downloaded from the GEO database using the platforms GPL18573, GPL24676, and GPL10558. DEGs were screened, WGCNA was performed as well as construction and analysis of PPI network. Functional enrichment analysis, GSEA, heat map of gene expression, survival analysis, and immune infiltration analysis were performed. The most relevant diseases to core genes were found by CTD. The GSE107943 dataset identified 3383 DEGs for cholangiocarcinoma, GSE47472 identified 95 DEGs for abdominal aortic aneurysm, and GSE213324 identified 10245 DEGs for renal cell carcinoma. For the GSE107943 cholangiocarcinoma dataset, GO analysis revealed enrichment in immune response, cell adhesion, extracellular space, and oxidoreductase activity. KEGG analysis indicated enrichment in metabolic pathways, the PI3K-Akt signaling pathway, cell apoptosis, the cell cycle, and the NF-kappa B signaling pathway. In the GSE47472 AAA dataset, GO analysis showed enrichment in neuroblast differentiation, cardiac muscle myofilament complex, and alkaline binding. KEGG analysis indicated enrichment in mRNA surveillance pathway and purine metabolism. In the GSE213324 renal cell carcinoma dataset, GO analysis indicated enrichment in immune system processes, cell adhesion, and membrane parts. KEGG analysis showed enrichment in cytokine-cytokine receptor interaction, calcium signaling pathway, and hematopoietic cell lineage. Furthermore, for cholangiocarcinoma (GSE107943), enriched terms associated with DEGs were in metabolic pathways, cell apoptosis, and the cell cycle. For AAA (GSE47472), enriched terms were in alkaline binding and cellular redox homeostasis. For renal cell carcinoma (GSE213324), enriched terms were in biological adhesion, regulation of immune system processes, and cell surface. Common core genes (ADH6, AGXT, CYP3A43, TYROBP) were identified for cholangiocarcinoma, renal cell carcinoma, and AAA. ADH6 and TYROBP were associated with cholangiocarcinoma, AAA, renal tumors, kidney diseases, atherosclerosis, and inflammation. TYROBP is abnormally expressed in cholangiocarcinoma, renal cancer and abdominal aortic aneurysm.

摘要

胆管癌发生于胆管系统的恶性肿瘤。肾细胞癌起源于肾小管上皮细胞。腹主动脉瘤(AAA)是由于腹主动脉壁的病变或损伤导致的永久性局部扩张。然而,TYROBP 与胆管癌、肾细胞癌和 AAA 之间的关系尚不清楚。从 GEO 数据库中使用平台 GPL18573、GPL24676 和 GPL10558 下载了胆管癌数据集 GSE107943、肾细胞癌数据集 GSE213324 和 AAA 数据集 GSE47472 的 DEGs,进行了 WGCNA 以及 PPI 网络的构建和分析。进行了功能富集分析、GSEA、基因表达热图、生存分析和免疫浸润分析。通过 CTD 找到与核心基因最相关的疾病。GSE107943 数据集确定了 3383 个胆管癌的 DEGs,GSE47472 确定了 95 个腹主动脉瘤的 DEGs,GSE213324 确定了 10245 个肾细胞癌的 DEGs。对于 GSE107943 胆管癌数据集,GO 分析显示免疫反应、细胞黏附、细胞外空间和氧化还原酶活性富集。KEGG 分析表明代谢途径、PI3K-Akt 信号通路、细胞凋亡、细胞周期和 NF-kappa B 信号通路富集。在 GSE47472 AAA 数据集,GO 分析显示神经母细胞分化、心肌肌球蛋白复合体和碱性结合富集。KEGG 分析表明 mRNA 监测途径和嘌呤代谢富集。在 GSE213324 肾细胞癌数据集,GO 分析显示免疫系统过程、细胞黏附、膜部分富集。KEGG 分析显示细胞因子-细胞因子受体相互作用、钙信号通路和造血细胞谱系富集。此外,对于胆管癌(GSE107943),与 DEGs 相关的富集术语与代谢途径、细胞凋亡和细胞周期有关。对于 AAA(GSE47472),富集术语为碱性结合和细胞氧化还原稳态。对于肾细胞癌(GSE213324),富集术语为生物黏附、免疫系统过程调节和细胞表面。确定了胆管癌(GSE107943)、肾细胞癌(GSE213324)和 AAA(GSE47472)的常见核心基因(ADH6、AGXT、CYP3A43、TYROBP)。ADH6 和 TYROBP 与胆管癌、AAA、肾肿瘤、肾脏疾病、动脉粥样硬化和炎症有关。TYROBP 在胆管癌、肾细胞癌和腹主动脉瘤中异常表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58bc/10766282/9cfa7c495eea/medi-103-e36843-g001.jpg

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