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新型蛋白质组提取方法揭示了微卫星高度不稳定（MSI-H）结直肠癌肿瘤保守的免疫特征。

Novel Proteome Extraction Method Illustrates a Conserved Immunological Signature of MSI-H Colorectal Tumors.

作者信息

Vainer Elez D, Kania-Almog Juliane, Zatara Ghadeer, Levin Yishai, Vainer Gilad W

机构信息

Department of Gastroenterology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

出版信息

Mol Cell Proteomics. 2020 Oct;19(10):1619-1631. doi: 10.1074/mcp.RA120.002152. Epub 2020 Jul 8.

DOI:10.1074/mcp.RA120.002152
PMID:32641473
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8015011/
Abstract

Using a simple, environment friendly proteome extraction (TOP), we were able to optimize the analysis of clinical samples. Using our TOP method we analyzed a clinical cohort of microsatellite stable (MSS) and unstable (MSI-H) colorectal carcinoma (CRC). We identified a tumor cell specific, STAT1-centered, immune signature expressed by the MSI-H tumor cells. We then showed that long, but not short, exposure to Interferon-γ induces a similar signature We identified 10 different temporal protein expression patterns, classifying the Interferon-γ protein temporal regulation in CRC. Our data sheds light on the changes that tumor cells undergo under long-term immunological pressure , the importance of STAT proteins in specific biological scenarios. The data generated could help find novel clinical biomarkers and therapeutic approaches.

摘要

通过使用一种简单、环保的蛋白质组提取方法（TOP），我们能够优化临床样本的分析。使用我们的TOP方法，我们分析了微卫星稳定（MSS）和不稳定（MSI-H）结直肠癌（CRC）的临床队列。我们鉴定出一种由MSI-H肿瘤细胞表达的肿瘤细胞特异性、以STAT1为中心的免疫特征。然后我们表明，长时间而非短时间暴露于干扰素-γ会诱导出类似的特征。我们鉴定出10种不同的蛋白质时间表达模式，对CRC中干扰素-γ蛋白的时间调控进行了分类。我们的数据揭示了肿瘤细胞在长期免疫压力下所经历的变化，以及STAT蛋白在特定生物学场景中的重要性。所产生的数据有助于找到新的临床生物标志物和治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec96/8015011/a6d9652d1b2d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec96/8015011/2ee6016a1934/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec96/8015011/a6d9652d1b2d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec96/8015011/2ee6016a1934/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec96/8015011/a6d9652d1b2d/gr2.jpg

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本文引用的文献

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PLoS One. 2020 Apr 10;15(4):e0229252. doi: 10.1371/journal.pone.0229252. eCollection 2020.
2
Myeloid maturation potentiates STAT3-mediated atypical IFN-γ signaling and upregulation of PD-1 ligands in AML and MDS.髓系成熟增强 STAT3 介导的非典型 IFN-γ 信号转导和 AML 及 MDS 中 PD-1 配体的上调。
Sci Rep. 2019 Aug 12;9(1):11697. doi: 10.1038/s41598-019-48256-4.
3
Fine-Tuning of Type I Interferon Response by STAT3.
STAT3 对 I 型干扰素反应的精细调控。
Front Immunol. 2019 Jun 26;10:1448. doi: 10.3389/fimmu.2019.01448. eCollection 2019.
4
Intrinsic Resistance to Immune Checkpoint Blockade in a Mismatch Repair-Deficient Colorectal Cancer.错配修复缺陷型结直肠癌中免疫检查点阻断的固有耐药性。
Cancer Immunol Res. 2019 Aug;7(8):1230-1236. doi: 10.1158/2326-6066.CIR-18-0683. Epub 2019 Jun 19.
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Update on proteomic studies of formalin-fixed paraffin-embedded tissues.关于福尔马林固定石蜡包埋组织的蛋白质组学研究进展。
Expert Rev Proteomics. 2019 Jun;16(6):513-520. doi: 10.1080/14789450.2019.1615452. Epub 2019 May 16.
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The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy.不断发展的免疫检查点抑制剂治疗生物标志物。
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