Genetics Department, Federal University of Parana, Curitiba, Brazil.
Functional Genomics Laboratory, Carlos Chagas Institute, Fiocruz, Curitiba, Parana, Brazil.
J Proteomics. 2019 May 15;199:1-14. doi: 10.1016/j.jprot.2019.02.007. Epub 2019 Feb 14.
Proteins play an essential role in the biological processes associated with cancer. Their altered expression levels can deregulate critical cellular pathways and interactive networks. In this study, the mass spectrometry-based label-free quantification followed by functional annotation was performed to investigate the most significant deregulated proteins among tissues of primary breast tumor (PT) and axillary metastatic lymph node (LN) and corresponding non-tumor tissues contralateral (NCT) and adjacent (ANT) from patients diagnosed with invasive ductal carcinoma. A total of 462 proteins was observed as differentially expressed (DEPs) among the groups analyzed. A high level of similarity was observed in the proteome profile of both non-tumor breast tissues and DEPs (n = 12) were mainly predicted in the RNA metabolism. The DEPs among the malignant and non-tumor breast tissues [n = 396 (PTxNCT) and n = 410 (LNxNCT)] were related to pathways of the LXR/RXR, NO, eNOS, eIF2 and sirtuins, tumor-related functions, fatty acid metabolism and oxidative stress. Remarkable similarity was observed between both malignant tissues, which the DEPs were related to metastatic capabilities. Altogether, our findings revealed differential proteomic profiles that affected cancer associated and interconnected signaling processes. Validation studies are recommended to demonstrate the potential of individual proteins and/or pathways as biological markers in breast cancer. SIGNIFICANCE: The proteomic analysis of this study revealed high similarity in the proteomic profile of the contralateral and adjacent non-tumor breast tissues. Significant differences were identified among the proteome of the malignant and non-tumor tissue groups of the same patients, providing relevant insights into the hallmarks, signaling pathways, biological functions, and interactive protein networks that act during tumorigenesis and breast cancer progression. These proteins are suggested as targets of relevant interest to be explored as potential biological markers related to tumor development and metastatic progression in the breast cancer disease.
蛋白质在与癌症相关的生物过程中发挥着至关重要的作用。它们表达水平的改变会使关键的细胞途径和相互作用网络失调。在这项研究中，采用基于质谱的无标记定量方法进行功能注释，以研究原发性乳腺癌（PT）和腋窝转移性淋巴结（LN）组织以及相应的对侧（NCT）和相邻（ANT）非肿瘤组织中差异表达最显著的蛋白质。在分析的各组中观察到 462 种蛋白质存在差异表达（DEPs）。两组非肿瘤乳腺组织和 DEPs（n=12）的蛋白质组谱具有高度相似性，主要预测涉及 RNA 代谢。恶性和非肿瘤乳腺组织[PTxNCT（n=396）和 LNxNCT（n=410）]之间的 DEPs 与 LXR/RXR、NO、eNOS、eIF2 和 sirtuins 途径、肿瘤相关功能、脂肪酸代谢和氧化应激有关。两种恶性组织之间存在显著的相似性，这些 DEPs 与转移能力有关。总之，我们的研究结果揭示了影响癌症相关和相互关联的信号转导过程的差异蛋白质组学特征。建议进行验证研究，以证明单个蛋白质和/或途径作为乳腺癌生物标志物的潜力。
本研究的蛋白质组学分析显示，对侧和相邻非肿瘤乳腺组织的蛋白质组谱具有高度相似性。在同一患者的恶性和非肿瘤组织组的蛋白质组中鉴定出显著差异，为肿瘤发生和乳腺癌进展过程中的特征、信号通路、生物学功能和相互作用蛋白质网络提供了相关见解。这些蛋白质被建议作为相关目标进行探索，作为与肿瘤发展和乳腺癌转移进展相关的潜在生物标志物。
