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UHRF1 在软组织肉瘤中的表达及临床意义及其预后价值。

The expression and clinical significance of UHRF1 in soft tissue sarcomas and its prognostic value.

机构信息

Department of Hepatobiliary Surgery, Neijiang First People's Hospital affiliated to Chongqing Medical University, Neijiang, China.

Department of Infection Management, Neijiang Hospital of Traditional Chinese Medicine affiliated to Chengdu University of Traditional Chinese Medicine, Neijiang, China.

出版信息

Medicine (Baltimore). 2024 Jun 7;103(23):e38393. doi: 10.1097/MD.0000000000038393.

DOI:10.1097/MD.0000000000038393
PMID:38847665
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11155523/
Abstract

To explore the expression and prognostic value of UHRF1 gene in soft tissue sarcoma (STS) and its related molecular mechanism. The expression data and clinicopathological parameters of STS were downloaded from the Cancer Genome Atlas (TCGA). The expression level of UHRF1 in STS and adjacent tissues and its relationship with clinicopathological characteristics were analyzed. The expression level of UHRF1 in STS tissues was significantly higher than that in paracancerous tissues (P < .001), and the overall survival (OS) time of patients with high UHRF1 expression was significantly shorter than that of patients with low UHRF1 expression (P = .002). The expression of UHRF1 was correlated with tumor necrosis, histological type and metastasis, and the differences were statistically significant (P = .013; P = .001; P = .002). The area ratio under receiver operating characteristic (ROC) curve between STS tissue and adjacent tissue of UHRF1 expression was 0.994. Number of tumors (HR = 0.416, 95%CI = 0.260-0.666, P < .001), depth of tumor (HR = 2.888, 95%CI = 0.910-9.168, P = .033), metastasis (HR = 2.888, 95% CI = 1.762-4.732, P < .001), residual tumor (HR = 2.637, 95% CI = 1.721-4.038, P < .001) and UHRF1 expression (HR = 1.342, 95% CI = 1.105-1.630, P = .003) were significantly associated with OS, and high expression of UHRF1 (HR = 1.387, 95%CI = 1.008-1.907, P = .044) was an independent risk factor for the prognosis of STS patients. The results of the nomogram exhibited that UHRF1 expression level had a significant effect on the total score value. GSEA enrichment analysis suggested that UHRF1 was involved in 14 signaling pathways regulating mRNA spliceosome, cell cycle, P53 signaling pathway were identified. Single sample gene set enrichment analysis (ssGSEA) exhibited that the expression of UHRF1 in STS was positively correlated with the level of Th2 cell infiltration, and negatively correlated with plasmacytoid dendritic cells (pDC), natural killer cells (NK), Eosinophils, Mast cells, etc. UHRF1 expression is involved in the immune microenvironment of HCC and affects the occurrence and development of HCC. UHRF1 is highly expressed in STS tissues. It is involved in the regulation of multiple tumor-related signaling pathways and immune cell microenvironment, suggesting that UHRF1 may be a potential molecular marker for prognosis prediction and targeted therapy of STS patients.

摘要

探讨泛素样含 PH 域蛋白 1(UHRF1)基因在软组织肉瘤(STS)中的表达及其预后价值及其相关分子机制。从癌症基因组图谱(TCGA)下载 STS 的表达数据和临床病理参数。分析 UHRF1 在 STS 和相邻组织中的表达水平及其与临床病理特征的关系。STS 组织中 UHRF1 的表达水平明显高于癌旁组织(P<0.001),高 UHRF1 表达患者的总生存期(OS)明显短于低 UHRF1 表达患者(P=0.002)。UHRF1 的表达与肿瘤坏死、组织学类型和转移有关,差异具有统计学意义(P=0.013;P=0.001;P=0.002)。UHRF1 表达的受试者工作特征(ROC)曲线下面积(AUC)在 STS 组织与相邻组织之间的比值为 0.994。肿瘤数量(HR=0.416,95%CI=0.260-0.666,P<0.001)、肿瘤深度(HR=2.888,95%CI=0.910-9.168,P=0.033)、转移(HR=2.888,95%CI=1.762-4.732,P<0.001)、残留肿瘤(HR=2.637,95%CI=1.721-4.038,P<0.001)和 UHRF1 表达(HR=1.342,95%CI=1.105-1.630,P=0.003)与 OS 显著相关,UHRF1 高表达(HR=1.387,95%CI=1.008-1.907,P=0.044)是 STS 患者预后的独立危险因素。列线图的结果表明 UHRF1 表达水平对总分值有显著影响。GSEA 富集分析表明,UHRF1 参与了 14 个调节 mRNA 剪接体、细胞周期、P53 信号通路的信号通路。单样本基因集富集分析(ssGSEA)表明,STS 中 UHRF1 的表达与 Th2 细胞浸润水平呈正相关,与浆细胞样树突状细胞(pDC)、自然杀伤细胞(NK)、嗜酸性粒细胞、肥大细胞等呈负相关。UHRF1 表达参与 HCC 的免疫微环境,影响 HCC 的发生发展。UHRF1 在 STS 组织中高表达。它参与了多个与肿瘤相关的信号通路和免疫细胞微环境的调节,表明 UHRF1 可能是预测 STS 患者预后和靶向治疗的潜在分子标志物。

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本文引用的文献

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Genetic and environmental reprogramming of the sarcoma epigenome.肉瘤表观基因组的遗传和环境重编程。
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UHRF1 associated with osteogenic differentiation of MSCs contributes to osteosarcoma progression and has clinical prognostic impact in osteosarcoma.UHRF1 与间充质干细胞的成骨分化有关,促进骨肉瘤的进展,并对骨肉瘤具有临床预后影响。
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UHRF1 modulates breast cancer cell growth via estrogen signaling.UHRF1 通过雌激素信号调节乳腺癌细胞的生长。
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Crosstalk between macrophage-derived PGE and tumor UHRF1 drives hepatocellular carcinoma progression.巨噬细胞衍生的 PGE 与肿瘤 UHRF1 之间的串扰驱动肝细胞癌进展。
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UHRF1 Could Be a Prognostic Biomarker and Correlated with Immune Cell Infiltration in Hepatocellular Carcinoma.UHRF1可能是一种预后生物标志物,且与肝细胞癌中的免疫细胞浸润相关。
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Dihydroartemisinin induces cell apoptosis through repression of UHRF1 in prostate cancer cells.双氢青蒿素通过抑制前列腺癌细胞中的 UHRF1 诱导细胞凋亡。
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UHRF1 Induces Methylation of the Promoter and Down-Regulates Gene Expression in Cervical Cancer.UHRF1 诱导宫颈癌启动子甲基化并下调基因表达。
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