化疗难治高级浆液性卵巢癌的蛋白质组学分析。
Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer.
发表日期：2023 Aug 03
作者：
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
来源：
CELL
摘要：
为了提高对化疗难治性高级别浆液卵巢癌（HGSOCs）的理解，我们对242例（难治和敏感）HGSOCs进行了蛋白质基因组学分析，涵盖了两种生物标本类型（固定在甲醛固定石蜡和冷冻）的一个发现组和两个验证组。我们确定了一个包含64种蛋白质的特征，可高度特异性地预测一部分对初始铂类治疗有抗药性的HGSOCs，并在两个独立的患者队列中进行了验证。我们发现17号染色体杂合性丧失（LOH）的缺乏与化疗抵抗性之间存在显著关联。基于通路蛋白表达，我们确定了5个HGSOC聚类，这些聚类在两个独立的患者队列和患者源异种移植模型中进行了验证。这些聚类可能代表了化疗抗性的不同机制，并涉及潜在的治疗敏感性。版权所有 © 2023年作者和Elsevier Inc.保留所有权利。
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.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.