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通过靶向质谱法对血浆蛋白进行多重定量以早期诊断胰腺导管腺癌

Multiplexed Quantitation of Plasma Proteins by Targeted Mass Spectrometry for Early Diagnosis of Pancreatic Ductal Adenocarcinoma.

作者信息

Korobkov Dmitry N, Molodtsov Ivan A, Kononikhin Alexey S, Bugrova Anna E, Indeykina Maria I, Brzhozovskiy Alexander G, Kanner Dmitry Yu, Nikolaev Evgeny N, Vasilieva Elena, Komissarov Alexey A

机构信息

Moscow City Oncology Hospital No. 62, 143515 Krasnogorsk, Russia.

I.V. Davydovsky Moscow City Clinical Hospital, Moscow Department of Healthcare, 117463 Moscow, Russia.

出版信息

Int J Mol Sci. 2025 Sep 21;26(18):9219. doi: 10.3390/ijms26189219.

Abstract

Pancreatic cancer (PC) is the sixth leading cause of cancer-related deaths worldwide. Patients with pancreatic ductal adenocarcinoma (PDAC), the most common type of PC, have a 5-year survival rate of approximately 10%. This low survival rate is mainly attributed to late-stage diagnoses and the lack of robust screening methods. Several serum proteins have been proposed as potential PDAC biomarkers, but they have not been introduced into clinical practice due to their low sensitivity and specificity. Therefore, the identification of new PDAC biomarkers remains highly important, and multiple reaction monitoring (MRM), a highly accurate mass spectrometry (MS) technique, can be used for this purpose. Using MRM MS analysis, we estimated the concentrations of 103 proteins in peripheral blood plasma from 132 participants: patients with newly diagnosed PDAC at different stages and healthy individuals. We identified six proteins that were differentially presented between healthy controls and patients with PDAC at all stages (adjusted -value < 0.01), and that were associated with survival rates for 23 months. A developed cross-validated model based on these six proteins showed an average accuracy of 90% in distinguishing between early-stage PDAC and healthy controls (AUC = 0.933). However, further research is needed to implement this model in clinical practice.

摘要

胰腺癌(PC)是全球癌症相关死亡的第六大主要原因。胰腺导管腺癌(PDAC)是PC最常见的类型,其患者的5年生存率约为10%。这种低生存率主要归因于晚期诊断和缺乏可靠的筛查方法。几种血清蛋白已被提议作为潜在的PDAC生物标志物,但由于其低敏感性和特异性,尚未被引入临床实践。因此,鉴定新的PDAC生物标志物仍然非常重要,多反应监测(MRM)作为一种高度准确的质谱(MS)技术,可用于此目的。通过MRM MS分析,我们估计了132名参与者外周血血浆中103种蛋白质的浓度:不同阶段新诊断的PDAC患者和健康个体。我们鉴定出六种蛋白质,它们在所有阶段的健康对照和PDAC患者之间存在差异表达(校正P值<0.01),并且与23个月的生存率相关。基于这六种蛋白质开发的交叉验证模型在区分早期PDAC和健康对照方面显示出90%的平均准确率(AUC = 0.933)。然而,需要进一步研究以在临床实践中应用该模型。

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