■乳腺癌是一个主要的公共卫生问题。蛋白质组学能够鉴定具有异常性质的蛋白质。这里,我们鉴定了乳腺癌组织中表达水平异常的蛋白质,并对数据进行了系统分析和验证,以确定潜在的诊断和治疗靶点.
通过等压标签相对和绝对定量(iTRAQ)技术检测乳腺癌组织和癌旁组织中的蛋白表达水平,并通过基因表达谱交互分析(GEPIA)数据库进一步筛选。细胞成分,进行蛋白质结构域和Reactome途径分析以筛选功能靶标。通过Oncomine数据库验证功能靶标的异常表达水平,定量实时聚合酶链反应(qRT-PCR)和蛋白质组学检测。进行蛋白相关性分析以解释乳腺癌中潜在目标的异常表达水平。
■总的来说,207和207蛋白质被上调和下调,分别,在乳腺癌组织中,在GEPIA数据库中也检测到约50%。重叠蛋白主要是白细胞粘附分子(EGF-Lam)结构域中含有表皮生长因子样结构域的细胞外蛋白,并富集在层粘连蛋白相互作用途径中。此外,下调的层粘连蛋白相互作用蛋白可能是功能靶标,这也通过Oncomine-Richardson和Oncomine-Curtis数据库进行了验证。然而,层粘连蛋白相互作用蛋白的较低表达水平仅适用于没有或低转移能力的管腔乳腺癌细胞,因为这些蛋白在更具侵袭性的claudin-low乳腺癌细胞中获得了较高的表达水平。此外,与相应的原位癌组织相比,上述蛋白质在浸润性癌组织中也显示出更高的表达水平。最后,我们已经揭示了层粘连蛋白相互作用蛋白和claudins之间的负相关。
■层粘连蛋白相互作用,特别是对于具有β1和γ1亚基的层粘连蛋白及其具有α1和α6亚基的整联蛋白受体,在没有转移能力或转移能力较低的管腔乳腺癌中显示较低的表达水平,但在具有较高转移能力的低claudin乳腺癌中表达水平较高;它们的高表达可能与claudin低表达有关。
UNASSIGNED: Breast cancer is a major public health concern. Proteomics enables identification of proteins with aberrant properties. Here, we identified proteins with abnormal expression levels in breast cancer tissues and systematically analyzed and validated the data to locate potential diagnostic and therapeutic targets.
UNASSIGNED: Protein expression level in breast cancer tissues and para-carcinoma tissues were detected by Isobaric Tags for Relative and Absolute Quantification (iTRAQ) technology and further screened through Gene Expression Profiling Interactive Analysis (GEPIA) database. Cellular components, protein domain and Reactome pathway analysis were performed to screen functional targets. Abnormal expression levels of functional targets were validated by Oncomine database, quantitative real time polymerase chain reaction (qRT-PCR) and proteomics detection. Protein correlation analysis was performed to explain the abnormal expression levels of potential targets in breast cancer.
UNASSIGNED: Overall, 207 and 207 proteins were up- and down-regulated, respectively, in breast cancer tissues, and approximately 50% were also detected in the GEPIA database. The overlapping proteins were mainly extracellular proteins containing epidermal growth factor-like domain in leukocyte adhesion molecule (EGF-Lam) domain and enriched in laminin interaction pathway. Moreover, the downregulated laminin interaction proteins could be functional targets, which were also validated through Oncomine-Richardson and Oncomine-Curtis database. However, the lower expression level of laminin interaction proteins only fit for luminal breast cancer cells with no or low metastasis ability because the proteins achieved higher expression level in more invasive claudin-low breast cancer cells. In addition, when compared with corresponding in situ carcinoma tissues, above-mentioned proteins also showed higher expression levels in invasive carcinoma tissues. Finally, we have revealed the negative correlation between the laminin interaction proteins and the claudins.
UNASSIGNED: The laminin interaction protein, especially for
laminins with β1 and γ1 subunits and their integrin receptors with α1 and α6 subunits, showed lower expression levels in luminal breast cancer with no or lower metastatic ability, but showed higher expression levels in claudin-low breast cancer with higher metastatic ability; and their higher expression could be related to the low claudin expression.