Genetic Pathology Evaluation Centre, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Interdisciplinary Oncology Program, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Nat Commun. 2022 Feb 16;13(1):896. doi: 10.1038/s41467-022-28524-0.
Despite advances in genomic classification of breast cancer, current clinical tests and treatment decisions are commonly based on protein level information. Formalin-fixed paraffin-embedded (FFPE) tissue specimens with extended clinical outcomes are widely available. Here, we perform comprehensive proteomic profiling of 300 FFPE breast cancer surgical specimens, 75 of each PAM50 subtype, from patients diagnosed in 2008-2013 (n = 178) and 1986-1992 (n = 122) with linked clinical outcomes. These two cohorts are analyzed separately, and we quantify 4214 proteins across all 300 samples. Within the aggressive PAM50-classified basal-like cases, proteomic profiling reveals two groups with one having characteristic immune hot expression features and highly favorable survival. Her2-Enriched cases separate into heterogeneous groups differing by extracellular matrix, lipid metabolism, and immune-response features. Within 88 triple-negative breast cancers, four proteomic clusters display features of basal-immune hot, basal-immune cold, mesenchymal, and luminal with disparate survival outcomes. Our proteomic analysis characterizes the heterogeneity of breast cancer in a clinically-applicable manner, identifies potential biomarkers and therapeutic targets, and provides a resource for clinical breast cancer classification.
尽管在乳腺癌的基因组分类方面取得了进展，但目前的临床检测和治疗决策通常基于蛋白质水平的信息。广泛可获得具有扩展临床结局的福尔马林固定石蜡包埋 (FFPE) 组织标本。在这里，我们对 300 个来自 2008-2013 年（n=178）和 1986-1992 年（n=122）诊断的患者的 75 个每种 PAM50 亚型的 300 个 FFPE 乳腺癌手术标本进行了全面的蛋白质组学分析，这些两个队列分别进行分析，我们定量分析了所有 300 个样本中的 4214 种蛋白质。在侵袭性 PAM50 分类的基底样病例中，蛋白质组学分析揭示了两组具有特征性免疫热点表达特征和高度有利的生存。Her2 富集病例分为具有不同细胞外基质、脂质代谢和免疫反应特征的异质组。在 88 例三阴性乳腺癌中，四个蛋白质组簇表现出基底免疫热点、基底免疫冷点、间充质和管腔的特征，具有不同的生存结果。我们的蛋白质组学分析以临床适用的方式描述了乳腺癌的异质性，确定了潜在的生物标志物和治疗靶点，并为临床乳腺癌分类提供了资源。
