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USP15 在乳腺癌转移与预后中重要性的调控网络分析

英文原题:A Regulatory Network Analysis of the Importance of USP15 in Breast Cancer Metastasis and Prognosis.

查看英文原题

A Regulatory Network Analysis of the Importance of USP15 in Breast Cancer Metastasis and Prognosis.

PubMed 2022/09/29(内容时间) J Oncol

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研究概要

这些发现表明 USP15 高表达提示 BRCA 预后不良,并揭示了潜在的调控网络及其与免疫浸润的正相关关系。

中文摘要

泛素特异性蛋白酶15(USP15)是USP家族中被发现的第16种蛋白酶,也是肿瘤发生过程中的关键蛋白。然而,USP15在乳腺癌中的预测价值和调控机制尚不清楚。

研究使用GEPIA、UALCAN、GeneMANIA和STRING数据库分析乳腺癌中USP15及其相关蛋白表达,并通过TIMER数据库评估免疫浸润模式。此外,采用蛋白质免疫印迹、细胞划痕、小室侵袭、三维基质胶、免疫沉淀和免疫组化(IHC)等实验研究USP15在乳腺癌中的调控机制。

包括GEPIA和UALCAN在内的多个数据库显示,乳腺癌中USP15总蛋白水平及其磷酸化均上调。USP15表达还与性别和临床分期显著相关。USP15高表达患者总生存期(OS)较短。功能网络分析显示,USP15可能通过TGF-β受体I参与肿瘤相关通路、DNA复制和细胞周期信号。此外,USP15表达与免疫评分、间质评分及多种TIL(肿瘤浸润淋巴细胞)浸润呈正相关。IHC结果进一步证实USP15在乳腺癌中的高表达及其潜在预后价值。

USP15高表达提示乳腺癌预后较差;研究还揭示了潜在调控网络及其与免疫浸润的正相关关系。因此,USP15可能是乳腺癌有吸引力的预测指标。

展开英文摘要原文

Ubiquitin-specific protease15(USP15), is the 16th identified protease in the USP family and is a key protein in tumorigenesis. However, the predictive value and regulatory mechanism of USP15 in breast cancer are unclear.

The GEPIA, UALCAN, GeneMANIA, and STRING databases were applied to explore the expression of USP15 in breast cancer and associated proteins. In addition, the TIMER database was evaluated for immune infiltration patterns. Moreover, protein immunoblotting assay, cell scratching assay, small compartment invasion assay, 3D stromal gel assay, immunoprecipitation assay, and immunohistochemistry (IHC) were used to USP15 regulatory mechanisms in breast cancer.

In BRCA, several databases, including GEPIA and UALCAN, describe the upregulation of total protein levels and USP15 phosphorylation. In addition, the expression of USP15 was significantly correlated with gender and clinical stage. Overall survival (OS) was lower in patients with high USP15 expression. Functional network analysis showed that USP15 is involved in tumor-associated pathways, DNA replication, and cell cycle signaling through TGF RI. In addition, USP15 expression was positively correlated with immune infiltration, including immune score, mesenchymal score, and several tumor-infiltrating lymphocytes (TIL). In addition, IHC results further confirmed the high expression of USP15 in breast cancer and its prognostic potential.

These findings demonstrate that high USP15 expression indicates poor prognosis in BRCA and reveal potential regulatory networks and the positive relationship with immune infiltration. Thus, USP15 may be an attractive predictor for BRCA.

论文信息

作者
Ling J、Qin C、Li T、Wang B、Cai W、Ma L、Wang Y、Chen J
单位
School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China.China
期刊
Journal of oncology2022
原文标识
PubMed 36213818 · DOI 10.1155/2022/1427726