肿瘤细胞治疗研究
英文原题：The expression and clinical significance of UHRF1 in soft tissue sarcomas and its prognostic value.
STS组织中UHRF1的表达水平显著高于癌旁组织（P < .001），UHRF1高表达患者的总生存期（OS）显著短于UHRF1低表达患者（P = .002）。
探讨UHRF1基因在软组织肉瘤（STS）中的表达、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及癌旁组织中的表达水平及其与临床病理特征的关系。UHRF1在STS组织中的表达水平显著高于癌旁组织（P < .001），UHRF1高表达患者的总生存期（OS）显著短于UHRF1低表达患者（P = .002）。UHRF1的表达与肿瘤坏死、组织学类型和转移相关，差异有统计学意义（P = .013；P = .001；P = .002）。UHRF1表达在STS组织与癌旁组织之间的受试者工作特征（ROC）曲线下面积比为0.994。肿瘤数目（HR = 0.416，95%CI = 0.260-0.666，P < .001）、肿瘤深度（HR = 2.888，95%CI = 0.910-9.168，P = .033）、转移（HR = 2.888，95% CI = 1.762-4.732，P < .001）、残留肿瘤（HR = 2.637，95% CI = 1.721-4.038，P < .001）和UHRF1表达（HR = 1.342，95% CI = 1.105-1.630，P = .003）与OS显著相关，UHRF1高表达（HR = 1.387，95%CI = 1.008-1.907，P = .044）是STS患者预后的独立危险因素。列线图结果显示，UHRF1表达水平对总分值有显著影响。GSEA富集分析提示，UHRF1参与了14条信号通路，鉴定出调控mRNA剪接体、细胞周期、P53信号通路。单样本基因集富集分析（ssGSEA）显示，UHRF1在STS中的表达与Th2细胞浸润水平呈正相关，与浆细胞样树突状细胞（pDC）、NK 细胞、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。它参与调控多个肿瘤相关信号通路和免疫细胞微环境，提示UHRF1可能是STS患者预后预测和靶向治疗的潜在分子标志物。
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.
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