Neagu Anca-Narcisa, Whitham Danielle, Buonanno Emma, Jenkins Avalon, Alexa-Stratulat Teodora, Tamba Bogdan Ionel, Darie Costel C
Biochemistry & Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University Potsdam, NY 13699-5810, USA.
Laboratory of Animal Histology, Faculty of Biology, "Alexandru Ioan Cuza" University of Iași Carol I bvd. No. 22, Iași 700505, Romania.
Am J Cancer Res. 2021 Sep 15;11(9):4006-4049. eCollection 2021.
Breast cancer is an individually unique, multi-faceted and chameleonic disease, an eternal challenge for the new era of high-integrated precision diagnostic and personalized oncomedicine. Besides traditional single-omics fields (such as genomics, epigenomics, transcriptomics and metabolomics) and multi-omics contributions (proteogenomics, proteotranscriptomics or reproductomics), several new "-omics" approaches and exciting proteomics subfields are contributing to basic and advanced understanding of these "": phenomics/cellomics, connectomics and interactomics, secretomics, matrisomics, exosomics, angiomics, chaperomics and epichaperomics, phosphoproteomics, ubiquitinomics, metalloproteomics, terminomics, degradomics and metadegradomics, adhesomics, stressomics, microbiomics, immunomics, salivaomics, materiomics and other biomics. Throughout the extremely complex neoplastic process, a Breast Cancer Cell Continuum Concept (BCCCC) has been modeled in this review as a spatio-temporal and holistic approach, as long as the breast cancer represents a complex cascade comprising successively integrated populations of heterogeneous tumor and cancer-associated cells, that reflect the carcinoma's progression from a "driving mutation" and formation of the breast primary tumor, toward the distant secondary tumors in different tissues and organs, via circulating tumor cell populations. This BCCCC is widely sustained by a Breast Cancer Proteomic Continuum Concept (BCPCC), where each phenotype of neoplastic and tumor-associated cells is characterized by a changing and adaptive proteomic profile detected in solid and liquid minimal invasive biopsies by complex proteomics approaches. Such a profile is created, beginning with the proteomic landscape of different neoplastic cell populations and cancer-associated cells, followed by subsequent analysis of protein biomarkers involved in epithelial-mesenchymal transition and intravasation, circulating tumor cell proteomics, and, finally, by protein biomarkers that highlight the extravasation and distant metastatic invasion. Proteomics technologies are producing important data in breast cancer diagnostic, prognostic, and predictive biomarkers discovery and validation, are detecting genetic aberrations at the proteome level, describing functional and regulatory pathways and emphasizing specific protein and peptide profiles in human tissues, biological fluids, cell lines and animal models. Also, proteomics can identify different breast cancer subtypes and specific protein and proteoform expression, can assess the efficacy of cancer therapies at cellular and tissular level and can even identify new therapeutic target proteins in clinical studies.
乳腺癌是一种独特、多面且多变的疾病，对于高度集成的精准诊断和个性化肿瘤医学新时代而言，它是一项永恒的挑战。除了传统的单组学领域（如基因组学、表观基因组学、转录组学和代谢组学）以及多组学贡献（蛋白质基因组学、蛋白质转录组学或生殖组学）之外，一些新的“组学”方法和令人兴奋的蛋白质组学子领域正在促进对乳腺癌的基础和深入理解：表型组学/细胞组学、连接组学和相互作用组学、分泌组学、基质组学、外泌体组学、血管组学、伴侣蛋白组学和表观伴侣蛋白组学、磷酸蛋白质组学、泛素组学、金属蛋白质组学、末端组学、降解组学和元降解组学、黏附组学、应激组学、微生物组学、免疫组学、唾液组学、材料组学和其他生物组学。在整个极其复杂的肿瘤发生过程中，本综述构建了一个乳腺癌细胞连续体概念（BCCCC），作为一种时空整体方法，因为乳腺癌代表了一个复杂的级联过程，依次包括异质性肿瘤细胞群和癌症相关细胞群，反映了癌症从“驱动突变”和乳腺原发性肿瘤形成，通过循环肿瘤细胞群，向不同组织和器官中的远处继发性肿瘤发展的过程。这个BCCCC得到了乳腺癌蛋白质组连续体概念（BCPCC）的广泛支持，其中肿瘤细胞和肿瘤相关细胞的每种表型都由通过复杂蛋白质组学方法在实体和液体微创活检中检测到的不断变化和适应性的蛋白质组图谱来表征。这样的图谱首先从不同肿瘤细胞群和癌症相关细胞的蛋白质组景观开始构建，随后分析参与上皮-间质转化和血管内渗的蛋白质生物标志物、循环肿瘤细胞蛋白质组学，最后分析突出血管外渗和远处转移侵袭的蛋白质生物标志物。蛋白质组学技术正在乳腺癌诊断、预后和预测生物标志物的发现与验证方面产生重要数据，在蛋白质组水平检测基因畸变，描述功能和调控途径，并强调人体组织、生物体液、细胞系和动物模型中的特定蛋白质和肽图谱。此外，蛋白质组学可以识别不同的乳腺癌亚型以及特定的蛋白质和蛋白质变体表达，可以在细胞和组织水平评估癌症治疗的疗效，甚至可以在临床研究中识别新的治疗靶点蛋白。
