【摘要】 背景与目的：垂体瘤转化基因1 (PTTG1)是一种癌基因，在多种肿瘤中高表达，可作为癌症侵袭转移的生物标志物。然而，PTTG1在乳腺癌中的表达水平及其与患者预后的关系并不清楚。本研究旨在研究乳腺癌中PTTG1的表达与患者预后的关系及其对免疫细胞浸润的影响，并初步探讨PTTG1在乳腺癌发生发展中的可能作用机制。方法：利用Oncomine 4.5数据库和Kaplan-Meier Plotter数据库分析乳腺癌组织中PTTG1的表达情况及其预测患者预后的价值。Coexpedia筛选出PTTG1的共表达基因，并通过GO数据库和KEGG数据库分析其共表达基因富集的通路情况。TIMER数据库用于分析乳腺癌中PTTG1基因表达水平与免疫细胞浸润的关系。采用multiMiR的R语言包预测与PTTG1及其共表达基因相互作用的microRNA，并使用Cytoscape进行网络可视化。结果：PTTG1在乳腺癌组织中表达明显升高，且高表达PTTG1患者的预后明显差于低表达PTTG1的患者（P<0.001）。乳腺癌中PTTG1基因及其共表达基因集GO功能主要富集在核分裂、细胞器分离及染色体分离上，KEGG通路富集则集中在细胞周期、减数分裂、人类T淋巴细胞白血病病毒Ⅰ型（HTLV-1）感染和p53信号转导通路上。PTTG1的表达水平与CD4+Th1细胞（r=0.490,P=3.52e-61）、CD4+Th2细胞（r=0.765,P=3.7e-192）、巨噬细胞（r=0.308,P=2.8e-23）、B细胞（r=0.228,P=3.69e-13）和中性粒细胞（r=0.121,P=1.27e-04）的浸润水平呈明显正相关，与CD8+T细胞浸润水平呈明显负相关（r=-0.198,P=3.16e-10）。用multiMiRR语言数据包分析发现共有17个共同靶向PTTG1及其共表达基因的microRNA。结论：PTTG1在乳腺癌组织高表达并与患者的不良预后相关，PTTG1在乳腺癌中的表达水平与免疫浸润密切相关。PTTG1高表达可能通过调控细胞周期和p53信号通路而使得肿瘤增殖和侵袭能力增强，进而导致乳腺癌的不良预后。PTTG1可能在乳腺癌中发挥癌基因的作用，提示PTTG1可以作为乳腺癌潜在的诊断和预后标记物。更多还原

【Abstract】 Background and Aims: Pituitary tumor transforming gene 1(PTTG1) is an oncogene highly expressed in various tumors and can be used as a biomarker for cancer invasion and metastasis. However, the expression level of PTTG1 in breast cancer and its relationship with the patient’s prognosis is unclear. This study was conducted to investigate the relationship between the expression of PTTG1 in breast cancer and the prognosis of patients and its effect on immune cell infiltration, and preliminarily explore the possible mechanism of PTTG1 in the occurrence and development of breast cancer.Methods: The expression of PTTG1 in breast cancer tissues and its prognostic value were analyzed using Oncomine 4.5 database and Kaplan-Meier Plotter database. The co-expressed genes of PTTG1 screened by Coexpedia and the enriched pathways by co-expressed genes were analyzed through GO and KEGG databases. TIMER database was used to analyze the relationship between PTTG1 gene expression level and immune cell infiltration in breast cancer. MultiMiR method of R language bundle was adopted to predict the microRNAs interacting with PTTG1 and its co-expressed genes, and Cytoscape was used for network visualization.Results: PTTG1 expression was significantly increased in breast cancer tissues, and the prognosis of patients with high PTTG1 expression was significantly worse than that of patients with low PTTG1 expression(P<0.001). In breast cancer, the GO function of PTTG1 gene and its co-expressed gene set was mainly enriched in nuclear division, organelle separation, and chromosome separation. In contrast, the KEGG pathway was enriched in cell cycle, meiosis, human T lymphocytic leukemia virus type I(HTLV-1) infection and p53 signal transduction pathway. The expression level of PTTG1 was significantly positively correlated with the infiltration level of CD4+ Th1 cells(r=0.490, P=3.52e-61), CD4+ Th2 cells(r=0.765, P=3.7e-192), macrophages(r=0.308, P=2.8e-23), B cells(r=0.228, P=3.69e-13) and neutrophils(r=0.121, P=1.27e-04), but was significantly negatively correlated with the infiltration level of CD8+ T cells(r=-0.198, P=3.16e-10). The multiMiR language data package analysis showed that there were 17 microRNAs co-targeting PTTG1 and its co-expressed genes.Conclusion: PTTG1 is highly expressed in breast cancer tissue and is associated with poor prognosis in patients. The expression level of PTTG1 in breast cancer is closely related to immune infiltration. High expression of PTTG1 may enhance tumor proliferation and invasion ability by regulating cell cycle and p53 signaling pathway, thereby leading to poor prognosis of breast cancer. PTTG1 may play an oncogene role in breast cancer, suggesting that PTTG1 can be used as a potential diagnostic and prognostic marker for breast cancer.更多还原