Wang Zijun, Wang Yinhuai, Peng Mou, Yi Lu
Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, China.
Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, China.
Front Oncol. 2020 Jan 15;9:1517. doi: 10.3389/fonc.2019.01517. eCollection 2019.
UBASH3B (STS1) is an important gene that negatively regulates T-cell receptor signaling in activated T-lymphocytes that involved in cancers. However, the function of UBASH3B in prostate cancer (PCa) and the correlation between UBASH3B and tumor-infiltrating immune cells still remain unclear. Real-time PCR and immunohistochemistry were applied to detect mRNA and protein expression of UBASH3B in PCa patients and benign prostate hyperplasia patients (BPH). Clinical features of patients with PCa were recorded and Kaplan Meier curve was subsequently plotted. Based on mRNA expression of UBASH3B, patients with PCa from TCGA database were divided into low-UBASH3B-expression group and high-UBASH3B-expression group for construct lncRNA-miRNA-mRNA network and analyzing GO and KEGG pathways. Single gene analysis method was performed by using GSEA to interpret gene expression data in PCa. The PPI network was constructed using STRING and the correlation between UBASH3B and tumor-infiltrating immune cells was analyzed by TIMER and CIBERSORT. The mRNA and protein expression of UBASH3B were upregulated in PCa. The abundant expression of UBASH3B is associated with poor prognosis in PCa. The subnetwork of UBASH3B contains three lncRNAs (MIAT, LINC01297, MYLK-AS1) and four miRNAs (hsa-miR-200a-3p, hsa-miR-455-5p, hsa-miR-192-5p, hsamiR- 215-5P). The mRNA expression of UBASH3B was involved in 28 KEGG pathways. GSEA analysis showed that 18 hallmark gene sets were significantly enriched in high-UBASH3B-expression, whereas 1 gene set was enriched in low-UBASH3B-expression. PPI network revealed a tightly interaction between UBASH3B and LCP2 (an immune related gene). TIMER and CIBERSORT database indicated that UBASH3B was correlated with 11 types of tumor-infiltrating immune cells (naïve B cell, memory B cells, resting CD4 memory T cell, activated CD4 memory T cell, regulatory T cell, activated NK cell, M2 macrophages, resting dendritic cells, activated dendritic cells, resting mast cells, neutrophils). In conclusion, UBASH3B may be a novel potential prognostic biomarker and is associated with tumor-infiltrating immune cells in tumor microenvironment, suggesting UBASH3B as a potential target for future treatment of PCa.
泛素相关SH3结构域蛋白3B（UBASH3B，又称STS1）是一个重要基因，它在参与癌症的活化T淋巴细胞中对T细胞受体信号传导起负调控作用。然而，UBASH3B在前列腺癌（PCa）中的功能以及UBASH3B与肿瘤浸润免疫细胞之间的相关性仍不清楚。应用实时聚合酶链反应（PCR）和免疫组织化学方法检测PCa患者和良性前列腺增生患者（BPH）中UBASH3B的mRNA和蛋白表达。记录PCa患者的临床特征，随后绘制Kaplan-Meier曲线。基于TCGA数据库中UBASH3B的mRNA表达，将PCa患者分为低UBASH3B表达组和高UBASH3B表达组，以构建lncRNA-miRNA-mRNA网络并分析基因本体（GO）和京都基因与基因组百科全书（KEGG）通路。使用基因集富集分析（GSEA）通过单基因分析方法解释PCa中的基因表达数据。利用STRING构建蛋白质-蛋白质相互作用（PPI）网络，并通过TIMER和CIBERSORT分析UBASH3B与肿瘤浸润免疫细胞之间的相关性。PCa中UBASH3B的mRNA和蛋白表达上调。UBASH3B的高表达与PCa的不良预后相关。UBASH3B的子网络包含三个长链非编码RNA（MIAT、LINC01297、MYLK-AS1）和四个微小RNA（hsa-miR-200a-3p、hsa-miR-455-5p、hsa-miR-192-5p、hsa-miR-215-5P）。UBASH3B的mRNA表达参与28条KEGG通路。GSEA分析显示，18个标志性基因集在高UBASH3B表达中显著富集，而1个基因集在低UBASH3B表达中富集。PPI网络揭示UBASH3B与LCP2（一个免疫相关基因）之间存在紧密相互作用。TIMER和CIBERSORT数据库表明，UBASH3B与11种肿瘤浸润免疫细胞（初始B细胞、记忆B细胞、静息CD4记忆T细胞、活化CD4记忆T细胞、调节性T细胞、活化自然杀伤细胞、M2巨噬细胞、静息树突状细胞、活化树突状细胞、静息肥大细胞、中性粒细胞）相关。总之，UBASH3B可能是一种新型潜在预后生物标志物，并且与肿瘤微环境中的肿瘤浸润免疫细胞相关，提示UBASH3B作为PCa未来治疗的潜在靶点。
