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乳腺癌中LAGEs家族基因特征分析及其预后相关性

Analysis of LAGEs Family Gene Signature and Prognostic Relevance in Breast Cancer.

作者信息

Khoa Ta Hoang Dang, Tang Wan-Chun, Phan Nam Nhut, Anuraga Gangga, Hou Sz-Ying, Chiao Chung-Chieh, Liu Yen-Hsi, Wu Yung-Fu, Lee Kuen-Haur, Wang Chih-Yang

机构信息

PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan.

Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.

出版信息

Diagnostics (Basel). 2021 Apr 19;11(4):726. doi: 10.3390/diagnostics11040726.

Abstract

Breast cancer (BRCA) is one of the most complex diseases and involves several biological processes. Members of the L-antigen (LAGE) family participate in the development of various cancers, but their expressions and prognostic values in breast cancer remain to be clarified. High-throughput methods for exploring disease progression mechanisms might play a pivotal role in the improvement of novel therapeutics. Therefore, gene expression profiles and clinical data of LAGE family members were acquired from the cBioportal database, followed by verification using the Oncomine and The Cancer Genome Atlas (TCGA) databases. In addition, the Kaplan-Meier method was applied to explore correlations between expressions of LAGE family members and prognoses of breast cancer patients. MetaCore, GlueGo, and GluePedia were used to comprehensively study the transcript expression signatures of LAGEs and their co-expressed genes together with LAGE-related signal transduction pathways in BRCA. The result indicated that higher LAGE3 messenger (m)RNA expressions were observed in BRCA tissues than in normal tissues, and they were also associated with the stage of BRCA patients. Kaplan-Meier plots showed that overexpression of LAGE1, LAGE2A, LAGE2B, and LAGE3 were highly correlated to poor survival in most types of breast cancer. Significant associations of LAGE family genes were correlated with the cell cycle, focal adhesion, and extracellular matrix (ECM) receptor interactions as indicated by functional enrichment analyses. Collectively, LAGE family members' gene expression levels were related to adverse clinicopathological factors and prognoses of BRCA patients; therefore, LAGEs have the potential to serve as prognosticators of BRCA patients.

摘要

乳腺癌(BRCA)是最复杂的疾病之一,涉及多个生物学过程。L抗原(LAGE)家族成员参与多种癌症的发展,但其在乳腺癌中的表达及预后价值仍有待阐明。探索疾病进展机制的高通量方法可能在新型治疗方法的改进中发挥关键作用。因此,从cBioportal数据库获取LAGE家族成员的基因表达谱和临床数据,随后使用Oncomine和癌症基因组图谱(TCGA)数据库进行验证。此外,应用Kaplan-Meier方法探讨LAGE家族成员的表达与乳腺癌患者预后之间的相关性。使用MetaCore、GlueGo和GluePedia全面研究LAGEs及其共表达基因的转录表达特征,以及它们在BRCA中与LAGE相关的信号转导途径。结果表明,在BRCA组织中观察到的LAGE3信使核糖核酸(mRNA)表达高于正常组织,并且它们还与BRCA患者的分期相关。Kaplan-Meier曲线显示,在大多数类型的乳腺癌中,LAGE1、LAGE2A、LAGE2B和LAGE3的过表达与较差的生存率高度相关。功能富集分析表明,LAGE家族基因与细胞周期、粘着斑和细胞外基质(ECM)受体相互作用存在显著关联。总体而言,LAGE家族成员的基因表达水平与BRCA患者的不良临床病理因素和预后相关;因此,LAGEs有潜力作为BRCA患者的预后指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4363/8074247/162a5b9f9f19/diagnostics-11-00726-g001.jpg

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