Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.
The John P. Murtha Cancer Center, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, USA.
J Pathol. 2018 Apr;244(5):628-637. doi: 10.1002/path.5036. Epub 2018 Feb 14.
Solid tumour malignancies comprise a highly variable admixture of tumour and non-tumour cellular populations, forming a complex cellular ecosystem and tumour microenvironment. This tumour heterogeneity is not incidental, and is known to correlate with poor patient prognosis for many cancer types. Indeed, non-malignant cell populations, such as vascular endothelial and immune cells, are known to play key roles supporting and, in some cases, driving aggressive tumour biology, and represent targets of emerging therapeutics, such as antiangiogenesis and immune checkpoint inhibitors. The biochemical interplay between these cellular populations and how they contribute to molecular tumour heterogeneity remains enigmatic, particularly from the perspective of the tumour proteome. This review focuses on recent advances in proteomic methods, namely imaging mass spectrometry, single-cell proteomic techniques, and preanalytical sample processing, that are uniquely positioned to enable detailed analysis of discrete cellular populations within tumours to improve our understanding of tumour proteomic heterogeneity. This review further emphasizes the opportunity afforded by the application of these techniques to the analysis of tumour heterogeneity in formalin-fixed paraffin-embedded archival tumour tissues, as these represent an invaluable resource for retrospective analyses that is now routinely accessible, owing to recent technological and methodological advances in tumour tissue proteomics. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
实体瘤恶性肿瘤包含高度可变的肿瘤和非肿瘤细胞群体混合物，形成复杂的细胞生态系统和肿瘤微环境。这种肿瘤异质性并非偶然，已知与许多癌症类型的患者预后不良相关。事实上，血管内皮和免疫细胞等非恶性细胞群体已被证实发挥着支持作用，在某些情况下还推动了侵袭性肿瘤生物学的发展，它们是新兴治疗方法（如抗血管生成和免疫检查点抑制剂）的作用靶点。这些细胞群体之间的生化相互作用及其对分子肿瘤异质性的贡献仍然是个谜，特别是从肿瘤蛋白质组学的角度来看。本文综述了蛋白质组学方法的最新进展，即成像质谱、单细胞蛋白质组学技术和样本预处理，这些方法非常适合对肿瘤内离散细胞群体进行详细分析，从而提高我们对肿瘤蛋白质组学异质性的认识。本文进一步强调了这些技术在分析福尔马林固定石蜡包埋存档肿瘤组织中的肿瘤异质性方面的应用机会，因为这些组织是回顾性分析的宝贵资源，由于肿瘤组织蛋白质组学的最新技术和方法进展，现在可以常规获得这些资源。版权所有©2018 英国和爱尔兰病理学学会。由 John Wiley & Sons, Ltd 出版。
