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通过基质辅助激光解吸电离质谱成像开发用于区分胰腺导管腺癌和胰腺神经内分泌肿瘤的类别预测模型

Development of a Class Prediction Model to Discriminate Pancreatic Ductal Adenocarcinoma from Pancreatic Neuroendocrine Tumor by MALDI Mass Spectrometry Imaging.

作者信息

Casadonte Rita, Kriegsmann Mark, Perren Aurel, Baretton Gustavo, Deininger Sören-Oliver, Kriegsmann Katharina, Welsch Thilo, Pilarsky Christian, Kriegsmann Jörg

机构信息

Proteopath GmbH, Trier, 54296, Germany.

Institute of Pathology, University of Heidelberg, Heidelberg, 69120, Germany.

出版信息

Proteomics Clin Appl. 2019 Jan;13(1):e1800046. doi: 10.1002/prca.201800046. Epub 2018 Dec 19.

Abstract

PURPOSE

To define proteomic differences between pancreatic ductal adenocarcinoma (pDAC) and pancreatic neuroendocrine tumor (pNET) by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI).

EXPERIMENTAL DESIGN

Ninety-three pDAC and 126 pNET individual tissues are assembled in tissue microarrays and analyzed by MALDI MSI. The cohort is separated in a training (52 pDAC and 83 pNET) and validation set (41 pDAC and 43 pNET). Subsequently, a linear discriminant analysis (LDA) model based on 46 peptide ions is performed on the training set and evaluated on the validation cohort. Additionally, two liver metastases and a whole slide of pDAC are analyzed by the same LDA algorithm.

RESULTS

Classification of pDAC and pNET by the LDA model is correct in 95% (39/41) and 100% (43/43) of patients in the validation cohort, respectively. The two liver metastases and the whole slide of pDAC are also correctly classified in agreement with the histopathological diagnosis.

CONCLUSION AND CLINICAL RELEVANCE

In the present study, a large dataset of pDAC and pNET by MALDI MSI is investigated, a class prediction model that allowed separation of both entities with high accuracy is developed, and differential peptide peaks with potential diagnostic, prognostic, and predictive values are highlighted.

摘要

目的

通过基质辅助激光解吸/电离质谱成像(MALDI MSI)确定胰腺导管腺癌(pDAC)和胰腺神经内分泌肿瘤(pNET)之间的蛋白质组差异。

实验设计

将93个pDAC和126个pNET个体组织组装到组织微阵列中,并通过MALDI MSI进行分析。该队列分为训练集(52个pDAC和83个pNET)和验证集(41个pDAC和43个pNET)。随后,在训练集上基于46个肽离子进行线性判别分析(LDA)模型,并在验证队列上进行评估。此外,通过相同的LDA算法分析了两个肝转移灶和一张pDAC全切片。

结果

在验证队列中,LDA模型对pDAC和pNET的分类分别在95%(39/41)和100%(43/43)的患者中是正确的。两个肝转移灶和pDAC全切片也与组织病理学诊断一致地被正确分类。

结论及临床意义

在本研究中,通过MALDI MSI研究了一个大型的pDAC和pNET数据集,开发了一个能够高精度分离这两种实体的类别预测模型,并突出了具有潜在诊断、预后和预测价值的差异肽峰。

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