富集的高级别浆液性卵巢癌肿瘤上皮细胞的蛋白质基因组分析确定了预后特征和治疗弱点。

Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities.

作者信息

Bateman Nicholas W, Abulez Tamara, Soltis Anthony R, McPherson Andrew, Choi Seongmin, Garsed Dale W, Pandey Ahwan, Tian Chunqiao, Hood Brian L, Conrads Kelly A, Teng Pang-Ning, Oliver Julie, Gist Glenn, Mitchell Dave, Litzi Tracy J, Tarney Christopher M, Crothers Barbara A, Mhawech-Fauceglia Paulette, Dalgard Clifton L, Wilkerson Matthew D, Pierobon Mariaelena, Petricoin Emanuel F, Yan Chunhua, Meerzaman Daoud, Bodelon Clara, Wentzensen Nicolas, Lee Jerry S H, Huntsman David G, Shah Sohrab, Shriver Craig D, Phippen Neil T, Darcy Kathleen M, Bowtell David D L, Conrads Thomas P, Maxwell G Larry

机构信息

Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD, USA.

出版信息

NPJ Precis Oncol. 2024 Mar 13;8(1):68. doi: 10.1038/s41698-024-00519-8.

DOI:10.1038/s41698-024-00519-8

PMID:38480868

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10937683/

Abstract

We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched tumor cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning a broad spectrum of purity. We identified patients with longer progression-free survival had increased immune-related signatures and validated proteins correlating with tumor-infiltrating lymphocytes in 65 tumors from an independent cohort of HGSOC patients, as well as with overall survival in an additional 126 HGSOC patient cohort. We identified that homologous recombination deficient (HRD) tumors are enriched in pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts. We further identified that polycomb complex protein BMI-1 is elevated in HR proficient (HRP) tumors, that elevated BMI-1 correlates with poor overall survival in HRP but not HRD HGSOC patients, and that HRP HGSOC cells are uniquely sensitive to BMI-1 inhibition.

摘要

我们对来自不同纯度范围的高级别浆液性卵巢癌（HGSOC）组织样本中的整块肿瘤以及激光显微切割富集的肿瘤细胞群体进行了深度蛋白质基因组分析。我们发现无进展生存期较长的患者具有增强的免疫相关特征，并在来自HGSOC患者独立队列的65个肿瘤中验证了与肿瘤浸润淋巴细胞相关的蛋白质，以及在另外126个HGSOC患者队列中验证了与总生存期相关的蛋白质。我们发现同源重组缺陷（HRD）肿瘤在与代谢和氧化磷酸化相关的途径中富集，我们在独立患者队列中对其进行了验证。我们进一步发现，多梳蛋白复合体蛋白BMI-1在同源重组 proficient（HRP）肿瘤中升高，BMI-1升高与HRP而非HRD的HGSOC患者的总生存期较差相关联，并且HRP的HGSOC细胞对BMI-1抑制具有独特的敏感性。