与炎症相关的结直肠癌血浆生物标志物的质谱蛋白质组学特征研究

IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Biomarker Insights Pub Date : 2024-06-20 eCollection Date: 2024-01-01 DOI:10.1177/11772719241257739
Víctor Urbiola-Salvador, Agnieszka Jabłońska, Dominika Miroszewska, Weronika Kamysz, Katarzyna Duzowska, Kinga Drężek-Chyła, Ronny Baber, René Thieme, Ines Gockel, Marek Zdrenka, Ewa Śrutek, Łukasz Szylberg, Michał Jankowski, Dariusz Bała, Wojciech Zegarski, Tomasz Nowikiewicz, Wojciech Makarewicz, Agnieszka Adamczyk, Aleksandra Ambicka, Marcin Przewoźnik, Agnieszka Harazin-Lechowska, Janusz Ryś, Katarzyna Macur, Paulina Czaplewska, Natalia Filipowicz, Arkadiusz Piotrowski, Jan P Dumanski, Zhi Chen
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引用次数: 0

摘要

背景:结肠直肠癌(CRC)的预后取决于疾病的分期,晚期患者的生存率很低。目前的 CRC 筛查项目主要使用结肠镜检查,但因其侵入性和高成本而受到限制。因此,迫切需要无创、经济、准确的替代方法:这项多中心血浆蛋白质组学回顾性研究通过高分辨率质谱蛋白质组学鉴定了 36 名 CRC 患者和 26 名健康志愿者血液中潜在的生物标志物,然后在一个独立的 CRC 队列(60 名 CRC 患者和 44 名健康受试者)中验证了所鉴定的生物标志物:结果:在 322 种已确定的血浆蛋白中,有 37 种在 CRC 患者和健康志愿者之间发生了变化,这些蛋白与补体级联、胆固醇代谢和 SERPIN 家族成员有关。首次发现 CRC 患者体内补体蛋白 C1QB、C4B 和 C5 以及促炎蛋白、脂多糖结合蛋白 (LBP) 和血清淀粉样蛋白 A4 组成型 (SAA4) 水平升高。重要的是,在一个独立验证的 CRC 队列中证实了 C5 水平的升高。C4B和C8A水平的升高与癌症相关炎症和CRC进展相关,而癌症相关炎症与急性期反应物富亮氨酸α-2-糖蛋白1(LRG1)和脑磷脂蛋白相关。此外,包括C4B、C8A、载脂蛋白C2(APO)C2和免疫球蛋白重常数γ2在内的4种蛋白质特征在早期和晚期CRC阶段之间发生了变化:我们的研究结果表明,C5 可能是诊断 CRC 的潜在生物标记物。进一步的验证研究将有助于应用这些新的潜在生物标记物来改善 CRC 诊断和患者护理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mass Spectrometry Proteomics Characterization of Plasma Biomarkers for Colorectal Cancer Associated With Inflammation.

Background: Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed.

Objective and design: This retrospective multi-center plasma proteomics study was performed to identify potential blood-based biomarkers in 36 CRC patients and 26 healthy volunteers by high-resolution mass spectrometry proteomics followed by the validation in an independent CRC cohort (60 CRC patients and 44 healthy subjects) of identified selected biomarkers.

Results: Among the 322 identified plasma proteins, 37 were changed between CRC patients and healthy volunteers and were associated with the complement cascade, cholesterol metabolism, and SERPIN family members. Increased levels in CRC patients of the complement proteins C1QB, C4B, and C5 as well as pro-inflammatory proteins, lipopolysaccharide-binding protein (LBP) and serum amyloid A4, constitutive (SAA4) were revealed for first time. Importantly, increased level of C5 was verified in an independent validation CRC cohort. Increased C4B and C8A levels were correlated with cancer-associated inflammation and CRC progression, while cancer-associated inflammation was linked to the acute-phase reactant leucine-rich alpha-2-glycoprotein 1 (LRG1) and ceruloplasmin. Moreover, a 4-protein signature including C4B, C8A, apolipoprotein C2 (APO) C2, and immunoglobulin heavy constant gamma 2 was changed between early and late CRC stages.

Conclusion: Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care.

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来源期刊
Biomarker Insights
Biomarker Insights MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.00
自引率
0.00%
发文量
26
审稿时长
8 weeks
期刊介绍: An open access, peer reviewed electronic journal that covers all aspects of biomarker research and clinical applications.
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