In silico investigation of heparanase-correlated genes in breast cancer subtypes

ABSTRACT Objective To investigate the possible genes that may be related to the mechanisms that modulate heparanase-1. Methods The analysis was conducted at Universidade Federal de São Paulo, on the data provided by: The Cancer Genome Atlas, University of California Santa Cruz Genome Browser, Kyoto Encyclopedia of Genes and Genomes Pathway Database, Database for Annotation, Visualization and Integrated Discovery Bioinformatics Database and the softwares cBioPortal and Ingenuity Pathway Analysis. Results Using messenger RNA expression pattern of different molecular subtypes of breast cancer, we proposed that heparinase-1 was co-related with its progression. In addition, genes that were analyzed presented co-expression with heparanase-1. The results that showed that heparanase-1 co-expressed with phosphoinositide 3-kinase adapter protein 1, sialic acid-binding immunoglobulin-like lectin 7, and leukocyte-associated immunoglobulin-like receptor 1 are directed related with immune system evasion during breast cancer progression. Furthermore, cathepsin L was co-expressed with heparanase-1 and transformed inactive heparanase-1 form into active heparanase-1, triggering extracellular matrix remodeling, which contributes to enhanced tumor-host interaction of the tumor. Conclusion The signaling pathway analysis using bioinformatics tools gives supporting evidence of possible mechanisms related to breast cancer development. Evasion genes of the immune system co-expressed with heparanase-1, a enzyme related with tumor progression.

摘要
研究目的：探讨可能调控乙酰肝素酶-1（heparanase-1）的相关机制及潜在关联基因。
方法：本研究于圣保罗联邦大学（Universidade Federal de São Paulo）开展，所用数据来源于癌症基因组图谱（The Cancer Genome Atlas）、加州大学圣克鲁兹分校基因组浏览器（University of California Santa Cruz Genome Browser）、京都基因与基因组百科全书通路数据库（Kyoto Encyclopedia of Genes and Genomes Pathway Database）、注释、可视化与整合发现生物信息学数据库（Database for Annotation, Visualization and Integrated Discovery Bioinformatics Database），以及cBioPortal和Ingenuity Pathway Analysis两款分析软件。
结果：本研究借助不同分子亚型乳腺癌的信使RNA（messenger RNA）表达谱，提出乙酰肝素酶-1与乳腺癌进展存在相关性。所纳入分析的基因均与乙酰肝素酶-1存在共表达现象；其中，与乙酰肝素酶-1共表达的磷酸肌醇3-激酶衔接蛋白1（phosphoinositide 3-kinase adapter protein 1）、唾液酸结合免疫球蛋白样凝集素7（sialic acid-binding immunoglobulin-like lectin 7）及白细胞相关免疫球蛋白样受体1（leukocyte-associated immunoglobulin-like receptor 1），与乳腺癌进展过程中的免疫逃逸直接相关。进一步研究发现，组织蛋白酶L（cathepsin L）可与乙酰肝素酶-1共表达，并能将无活性的乙酰肝素酶-1转化为活性形式，进而触发细胞外基质重塑，促进肿瘤与宿主间的相互作用增强。
结论：采用生物信息学工具开展的信号通路分析，为乳腺癌发生发展的潜在相关机制提供了佐证。与乙酰肝素酶-1共表达的免疫逃逸基因，以及作为肿瘤进展相关酶类的乙酰肝素酶-1本身，均与乳腺癌进展密切相关。