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凝血酶原的激活在结直肠癌进展中似乎比补体系统发挥更早的作用:一项质谱评估。

The Activation of Prothrombin Seems to Play an Earlier Role than the Complement System in the Progression of Colorectal Cancer: A Mass Spectrometry Evaluation.

作者信息

Beitia Maider, Romano Paolo, Larrinaga Gorka, Solano-Iturri Jon Danel, Salis Annalisa, Damonte Gianluca, Bruzzone Marco, Ceppi Marcello, Profumo Aldo

机构信息

Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Biscay, Spain.

Proteomics and Mass Spectrometry Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.

出版信息

Diagnostics (Basel). 2020 Dec 11;10(12):1077. doi: 10.3390/diagnostics10121077.

DOI:10.3390/diagnostics10121077
PMID:33322644
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7763171/
Abstract

Colorectal cancer (CRC) is the second cause of death in men and the third in women. This work deals with the study of the low molecular weight protein fraction of sera from patients who underwent surgery for CRC and who were followed for several years thereafter. MALDI-TOF MS was used to identify serum peptidome profiles of healthy controls, non-metastatic CRC patients and metastatic CRC patients. A multiple regression model was applied to signals preliminarily selected by SAM analysis to take into account the age and gender differences between the groups. We found that, while a signal m/z 2021.08, corresponding to the C3f fragment of the complement system, appears significantly increased only in serum from metastatic CRC patients, a m/z 1561.72 signal, identified as a prothrombin fragment, has a significantly increased abundance in serum from non-metastatic patients as well. The findings were also validated by a bootstrap resampling procedure. The present results provide the basis for further studies on large cohorts of patients in order to confirm C3f and prothrombin as potential serum biomarkers. Thus, new and non-invasive tests might be developed to improve the classification of colorectal cancer.

摘要

结直肠癌(CRC)是男性第二大致死原因,女性第三大致死原因。本研究针对接受CRC手术并随访数年的患者血清中的低分子量蛋白质组分展开。基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)用于鉴定健康对照、非转移性CRC患者和转移性CRC患者的血清肽组图谱。采用多元回归模型对通过SAM分析初步筛选出的信号进行分析,以考虑各组之间的年龄和性别差异。我们发现,虽然对应补体系统C3f片段的m/z 2021.08信号仅在转移性CRC患者血清中显著升高,但鉴定为凝血酶原片段的m/z 1561.72信号在非转移性患者血清中的丰度也显著增加。研究结果还通过自助重采样程序得到验证。目前的结果为进一步研究大量患者队列提供了基础,以确认C3f和凝血酶原作为潜在的血清生物标志物。因此,可能会开发新的非侵入性检测方法来改善结直肠癌的分类。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaf/7763171/30a7745f3894/diagnostics-10-01077-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaf/7763171/ccdd30d757ea/diagnostics-10-01077-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaf/7763171/6c6d9fd3ed8f/diagnostics-10-01077-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaf/7763171/30a7745f3894/diagnostics-10-01077-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaf/7763171/ccdd30d757ea/diagnostics-10-01077-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaf/7763171/6c6d9fd3ed8f/diagnostics-10-01077-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaf/7763171/30a7745f3894/diagnostics-10-01077-g003.jpg

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本文引用的文献

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Front Immunol. 2018 Nov 20;9:2664. doi: 10.3389/fimmu.2018.02664. eCollection 2018.
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Mechanisms coupling thrombin to metastasis and tumorigenesis.将凝血酶与转移和肿瘤发生相偶联的机制。
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Complement 5a stimulates macrophage polarization and contributes to tumor metastases of colon cancer.
基于RNA测序的慢传输型便秘关键基因分析
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A Circulating Risk Score, Based on Combined Expression of Exo-miR-130a-3p and Fibrinopeptide A, as Predictive Biomarker of Relapse in Resectable Non-Small Cell Lung Cancer Patients.基于外泌体miR-130a-3p和纤维蛋白肽A联合表达的循环风险评分,作为可切除非小细胞肺癌患者复发的预测生物标志物。
Cancers (Basel). 2022 Jul 14;14(14):3412. doi: 10.3390/cancers14143412.
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Inside-Out of Complement in Cancer.补体系统在癌症中的内-外作用。
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GeenaR: A Web Tool for Reproducible MALDI-TOF Analysis.吉娜R:用于可重复基质辅助激光解吸电离飞行时间分析的网络工具。
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补体 5a 可刺激巨噬细胞极化,并有助于结肠癌的肿瘤转移。
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A mass spectrometry based method and a software tool to assess degradation status of serum samples to be used in proteomics for biomarker discovery.一种基于质谱分析的方法和软件工具,用于评估蛋白质组学中用于生物标志物发现的血清样本的降解状态。
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