近日，美国福瑞德·哈金森癌症研究中心Amanda G. Paulovich等研究人员合作完成化疗难治型高级别浆液性卵巢癌的蛋白质基因组分析。该研究于2023年8月3日发表于国际一流学术期刊《细胞》。
为了加深对化疗难治型高级别浆液性卵巢癌（HGSOC）的了解，研究人员描述了242例（难治型和敏感型）HGSOCs的蛋白质基因组图谱，它们代表了两种生物样本类型（福尔马林固定石蜡包埋和冷冻）的一个发现队列和两个验证队列。研究人员发现了一种64个蛋白的特征，该特征能高度特异性地预测对初始铂类疗法难治的HGSOC亚群，并在两个独立的患者队列中得到了验证。
研究人员发现缺乏Ch17杂合性缺失（LOH）与化疗难治型之间存在明显关联。基于通路蛋白表达，研究人员确定了5个HGSOC群，并在两个独立的患者队列和患者异种移植（PDX）模型中得到了验证。这些集群可能代表了不同的耐药机制，并牵涉到可能的治疗漏洞。
附：英文原文
Title: Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer
Author: Shrabanti Chowdhury, Jacob J. Kennedy, Richard G. Ivey, Oscar D. Murillo, Noshad Hosseini, Xiaoyu Song, Francesca Petralia, Anna Calinawan, Sara R. Savage, Anna B. Berry, Boris Reva, Umut Ozbek, Azra Krek, Weiping Ma, Felipe da Veiga Leprevost, Jiayi Ji, Seungyeul Yoo, Chenwei Lin, Uliana J. Voytovich, Yajue Huang, Sun-Hee Lee, Lindsay Bergan, Travis D. Lorentzen, Mehdi Mesri, Henry Rodriguez, Andrew N. Hoofnagle, Zachary T. Herbert, Alexey I. Nesvizhskii, Bing Zhang, Jeffrey R. Whiteaker, David Fenyo, Wilson McKerrow, Joshua Wang, Stephan C. Schürer, Vasileios Stathias, X. Steven Chen, Mary Helen Barcellos-Hoff, Timothy K. Starr, Boris J. Winterhoff, Andrew C. Nelson, Samuel C. Mok, Scott H. Kaufmann, Charles Drescher, Marcin Cieslik, Pei Wang, Michael J. Birrer, Amanda G. Paulovich
Issue&Volume: 2023/08/03
Abstract: To improve the understanding of chemo-refractory high-grade serous ovarian cancers (HGSOCs), we characterized the proteogenomic landscape of 242 (refractory and sensitive) HGSOCs, representing one discovery and two validation cohorts across two biospecimen types (formalin-fixed paraffin-embedded and frozen). We identified a 64-protein signature that predicts with high specificity a subset of HGSOCs refractory to initial platinum-based therapy and is validated in two independent patient cohorts. We detected significant association between lack of Ch17 loss of heterozygosity (LOH) and chemo-refractoriness. Based on pathway protein expression, we identified 5 clusters of HGSOC, which validated across two independent patient cohorts and patient-derived xenograft (PDX) models. These clusters may represent different mechanisms of refractoriness and implicate putative therapeutic vulnerabilities.
DOI: 10.1016/j.cell.2023.07.004
Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00737-7