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16 种主要人类癌症的蛋白质组学特征揭示了通用和癌症类型特异性蛋白质,可用于鉴定潜在的治疗靶点。

Proteomic signatures of 16 major types of human cancer reveal universal and cancer-type-specific proteins for the identification of potential therapeutic targets.

机构信息

Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, 21231, USA.

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.

出版信息

J Hematol Oncol. 2020 Dec 7;13(1):170. doi: 10.1186/s13045-020-01013-x.

DOI:10.1186/s13045-020-01013-x
PMID:33287876
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7720039/
Abstract

BACKGROUND

Proteomic characterization of cancers is essential for a comprehensive understanding of key molecular aberrations. However, proteomic profiling of a large cohort of cancer tissues is often limited by the conventional approaches.

METHODS

We present a proteomic landscape of 16 major types of human cancer, based on the analysis of 126 treatment-naïve primary tumor tissues, 94 tumor-matched normal adjacent tissues, and 12 normal tissues, using mass spectrometry-based data-independent acquisition approach.

RESULTS

In our study, a total of 8527 proteins were mapped to brain, head and neck, breast, lung (both small cell and non-small cell lung cancers), esophagus, stomach, pancreas, liver, colon, kidney, bladder, prostate, uterus and ovary cancers, including 2458 tissue-enriched proteins. Our DIA-based proteomic approach has characterized major human cancers and identified universally expressed proteins as well as tissue-type-specific and cancer-type-specific proteins. In addition, 1139 therapeutic targetable proteins and 21 cancer/testis (CT) antigens were observed.

CONCLUSIONS

Our discoveries not only advance our understanding of human cancers, but also have implications for the design of future large-scale cancer proteomic studies to assist the development of diagnostic and/or therapeutic targets in multiple cancers.

摘要

背景

对癌症进行蛋白质组学特征分析对于全面了解关键的分子异常至关重要。然而,传统方法常常限制了对大量癌症组织进行蛋白质组学分析。

方法

我们使用基于质谱的无数据依赖采集方法,对 126 例未经治疗的原发性肿瘤组织、94 例肿瘤匹配的正常相邻组织和 12 例正常组织进行了分析,呈现了 16 种主要类型人类癌症的蛋白质组图谱。

结果

在我们的研究中,共将 8527 种蛋白质映射到脑、头颈部、乳腺、肺(小细胞肺癌和非小细胞肺癌)、食管、胃、胰腺、肝、结肠、肾、膀胱、前列腺、子宫和卵巢癌,包括 2458 种组织丰富蛋白。我们基于 DIA 的蛋白质组学方法对主要的人类癌症进行了特征描述,并鉴定了普遍表达的蛋白以及组织特异性和癌症特异性蛋白。此外,还观察到 1139 种治疗靶点蛋白和 21 种癌症/睾丸(CT)抗原。

结论

我们的发现不仅推进了我们对人类癌症的理解,而且还为未来大规模癌症蛋白质组学研究的设计提供了参考,以协助多种癌症的诊断和/或治疗靶点的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4382/7720579/106917de8e5c/13045_2020_1013_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4382/7720579/8d6fd79f8a3c/13045_2020_1013_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4382/7720579/75e921f73447/13045_2020_1013_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4382/7720579/5e0c2b12255e/13045_2020_1013_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4382/7720579/822fc7857fac/13045_2020_1013_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4382/7720579/bbefc4ac2d05/13045_2020_1013_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4382/7720579/106917de8e5c/13045_2020_1013_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4382/7720579/8d6fd79f8a3c/13045_2020_1013_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4382/7720579/75e921f73447/13045_2020_1013_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4382/7720579/5e0c2b12255e/13045_2020_1013_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4382/7720579/822fc7857fac/13045_2020_1013_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4382/7720579/bbefc4ac2d05/13045_2020_1013_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4382/7720579/106917de8e5c/13045_2020_1013_Fig6_HTML.jpg

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