乳腺癌中垂体瘤转化基因1对免疫浸润的影响及其预后价值
作者:
通讯作者:
作者单位:

广州市红十字会医院/暨南大学附属广州红十字会医院 超声科,广东 广州 510220

作者简介:

曾宝辉,广东省广州市红十字会医院/暨南大学附属广州红十字会医院主治医师,主要从事乳腺癌的临床基础方面的研究。

基金项目:

广东省科技厅科技发展专项基金资助项目(2016A020215015)。


Effect of pituitary tumor transforming gene 1 on immune infiltration in breast cancer and its prognostic value
Author:
Affiliation:

Department of Ultrasound Diagnostics, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou 510220, China

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 音频文件
  • |
  • 视频文件
    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multiMiR R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。

    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.

    图1 乳腺癌中PTTG1 mRNA的表达水平及其与患者生存率的关系 A-D:在Curtis Breast、Richardson Breast、TCGA Breast和Zhao Breast数据集中乳腺肿瘤组织和正常乳腺组织之间PTTG1 mRNA表达水平的差异;E:TCGA数据集中乳腺肿瘤组织和正常乳腺组织之间PTTG1 DNA拷贝数的差异;F:Kaplan-Meier生存曲线分析PTTG1表达高低对总生存率的影响(n=1 402)Fig.1 The expression level of PTTG1 mRNA in breast cancer tissues and its relationship with survival rate of patients A-D: The differences of PTTG1 mRNA expression levels between breast tumor tissues and normal breast tissues in the Curtis Breast, Richardson Breast, TCGA Breast and Zhao Breast datasets; E: The difference in PTTG1 DNA copy number between breast tumor tissues and normal breast tissues in the TCGA dataset; F: Analysis the influence of PTTG1 expression level on overall survival rate with Kaplan-Meier survival curve (n=1 402)
    图2 PTTG1的表达与乳腺癌临床病理特征的关系 A:PTTG1在不同临床分期乳腺癌组织中的相对表达水平;B:PTTG1在不同种族乳腺癌患者中的相对表达水平;C:PTTG1在不同年龄段乳腺癌患者中的相对表达水平;D:PTTG1在不同TP53状态的乳腺癌患者中的相对表达水平;E:PTTG1在不同淋巴结转移状态乳腺癌患者中的相对表达水平;F:正常乳腺组织标本和乳腺癌组织标本中PTTG1 mRNA表达水平的箱线图Fig.2 Correlation between PTTG1 expression and clinicopathologic features in breast cancer A: The relative expression level of PTTG1 in breast cancer tissues with different clinical stages; B: The relative expression level of PTTG1 in breast cancer patients with different races; C: The relative expression levels of PTTG1 in breast cancer patients with different ages; D: The relative expression level of PTTG1 in breast cancer patients with different TP53 status; E: The relative expression level of PTTG1 in breast cancer patients with different status of lymph node metastasis; F: Boxplots of PTTG1 mRNA expression levels in normal and breast cancer tissues
    图3 PTTG1的共表达基因网络(PTTG1用红色圆圈标识,共表达基因用绿色圆圈标注)Fig.3 Co-expression gene network of PTTG1 (PTTG1 marked by red circles, and the co-expressed genes marked by green circles)
    图4 乳腺癌中PTTG1共表达基因的GO和KEGG通路富集分析 A:PTTG1及其共表达基因的分子功能作用;B:PTTG1及其共表达基因在细胞成分中的作用;C:PTTG1及其共表达基因所参与的生物学过程;D:PTTG1及其共表达基因的KEGG相关通路;E:细胞周期通路网络(共表达基因在此通路中所在的位置以红色标注)Fig.4 Enrichment analysis of GO and KEGG pathways of PTTG1 co-expressed genes in breast cancer A: Molecular functional roles of PTTG1 and its co-expressed genes; B: The role of PTTG1 and its co-expressed genes in cell components; C: Biological processes involved in PTTG1 and its co-expressed genes; D: KEGG related pathways of PTTG1 and its co-expressed genes; E: Network of cell cycle pathway (the locations of co-expressed genes in this pathway indicated in red)
    图5 乳腺癌中PTTG1共表达基因和通路的可视化网络 A:PTTG1共表达基因可视化网络; B:共表达基因的KEGG通路富集可视化网络Fig.5 Visual network of PTTG1 co-expressed genes and pathways in breast cancer A: Visual network of PTTG1 co-expressed genes; B: Visual network of KEGG pathway enrichment in co-expressed genes
    图6 PTTG1表达水平与浸润性免疫细胞浸润水平的关系 A-F:PTTG1的表达与CD4+ Th1细胞、CD4+ Th2细胞、巨噬细胞、CD8+ T细胞、B细胞和中性粒细胞浸润水平呈正相关,与CD8+ T细胞浸润程度呈负相关Fig.6 Relationship between the expression level of PTTG1 and the infiltration level of infiltrating immune cells A-F: The expression of PTTG1 positively correlated with the infiltration levels of CD4+ Th1 cells, CD4+ Th2 cells, macrophages, CD8+ T cells, B cells and neutrophils, and negatively correlated with the infiltration degree of CD8+ T cells
    图7 PTTG1-microRNA-共表达基因可视化网络Fig.7 Visualization network of PTTG1-microRNA-Co-expression genes
    参考文献
    相似文献
    引证文献
引用本文

曾宝辉,过新民,郭顺华.乳腺癌中垂体瘤转化基因1对免疫浸润的影响及其预后价值[J].中国普通外科杂志,2022,31(11):1483-1492.
DOI:10.7659/j. issn.1005-6947.2022.11.010

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
历史
  • 收稿日期:2021-04-25
  • 最后修改日期:2022-04-08
  • 录用日期:
  • 在线发布日期: 2022-12-07