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上皮性卵巢癌的蛋白质组学特征分析明确了不同组织学亚型的分子特征和治疗靶点。

Proteomic characterization of epithelial ovarian cancer delineates molecular signatures and therapeutic targets in distinct histological subtypes.

机构信息

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

出版信息

Nat Commun. 2023 Nov 28;14(1):7802. doi: 10.1038/s41467-023-43282-3.

DOI:10.1038/s41467-023-43282-3
PMID:38016970
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10684593/
Abstract

Clear cell carcinoma (CCC), endometrioid carcinoma (EC), and serous carcinoma (SC) are the major histological subtypes of epithelial ovarian cancer (EOC), whose differences in carcinogenesis are still unclear. Here, we undertake comprehensive proteomic profiling of 80 CCC, 79 EC, 80 SC, and 30 control samples. Our analysis reveals the prognostic or diagnostic value of dysregulated proteins and phosphorylation sites in important pathways. Moreover, protein co-expression network not only provides comprehensive view of biological features of each histological subtype, but also indicates potential prognostic biomarkers and progression landmarks. Notably, EOC have strong inter-tumor heterogeneity, with significantly different clinical characteristics, proteomic patterns and signaling pathway disorders in CCC, EC, and SC. Finally, we infer MPP7 protein as potential therapeutic target for SC, whose biological functions are confirmed in SC cells. Our proteomic cohort provides valuable resources for understanding molecular mechanisms and developing treatment strategies of distinct histological subtypes.

摘要

透明细胞癌(CCC)、子宫内膜样癌(EC)和浆液性癌(SC)是卵巢上皮性癌(EOC)的主要组织学亚型,其发生机制的差异尚不清楚。在这里,我们对 80 个 CCC、79 个 EC、80 个 SC 和 30 个对照样本进行了全面的蛋白质组学分析。我们的分析揭示了失调蛋白和重要途径中磷酸化位点的预后或诊断价值。此外,蛋白质共表达网络不仅提供了每个组织学亚型的生物学特征的全面视图,还指出了潜在的预后生物标志物和进展标志。值得注意的是,EOC 具有很强的肿瘤间异质性,在 CCC、EC 和 SC 中具有明显不同的临床特征、蛋白质组学模式和信号通路紊乱。最后,我们推断 MPP7 蛋白可能是 SC 的潜在治疗靶点,其在 SC 细胞中的生物学功能得到了证实。我们的蛋白质组学队列为理解不同组织学亚型的分子机制和开发治疗策略提供了有价值的资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8d/10684593/dfc53f5b2651/41467_2023_43282_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8d/10684593/943b123e20c2/41467_2023_43282_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8d/10684593/9ff90abc4ad7/41467_2023_43282_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8d/10684593/31f3cb607d5d/41467_2023_43282_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8d/10684593/cbf8f8f3dda0/41467_2023_43282_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8d/10684593/5d165fd8aa2c/41467_2023_43282_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8d/10684593/dfc53f5b2651/41467_2023_43282_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8d/10684593/943b123e20c2/41467_2023_43282_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8d/10684593/9ff90abc4ad7/41467_2023_43282_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8d/10684593/31f3cb607d5d/41467_2023_43282_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8d/10684593/cbf8f8f3dda0/41467_2023_43282_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8d/10684593/5d165fd8aa2c/41467_2023_43282_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8d/10684593/dfc53f5b2651/41467_2023_43282_Fig6_HTML.jpg

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