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甲状腺微小乳头状癌侧方淋巴结转移相关组织蛋白的蛋白质组学分析

Proteomic Analysis of Tissue Proteins Related to Lateral Lymph Node Metastasis in Papillary Thyroid Microcarcinoma.

作者信息

Zhang Qiyao, Cao Zhen, Wang Yuanyang, Wu Hao, Zhang Zejian, Liu Ziwen

机构信息

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P. R. China.

Institute of Clinical Medicine, State Key Laboratory of Complex Severe and Rare Diseases, National Infrastructure for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P. R. China.

出版信息

J Proteome Res. 2025 Jan 3;24(1):256-267. doi: 10.1021/acs.jproteome.4c00737. Epub 2024 Nov 27.

Abstract

Patients with lateral lymph node metastasis (LLNM) may experience higher locoregional recurrence rates and poorer prognoses compared to those without LLNM, highlighting the need for effective preoperative stratification to reliably assess risk LLNM. In this study, we collected PTMC samples from Peking Union Medical College Hospital and employed data-independent acquisition mass spectrometry proteomics technique to identify protein profiles in PTMC tissues with and without LLNM. Pseudo temporal analysis and single sample gene set enrichment analysis were conducted in combination with The Cancer Genome Atlas Thyroid Carcinoma for functional coordination analysis and the construction of a prediction model based on random forest. Non-negative matrix factorization (NMF) clustering was utilized to classify molecular subtypes of PTMC. Our findings revealed that the differential activation of pathways such as MAPK and PI3K was critical in enhancing the lateral lymph node metastatic potential of PTMC. We successfully screened biomarkers via machine learning and public databases, creating an effective prediction model for metastasis. Additionally, we explored the mechanism of metastasis-associated PTMC subtypes via NMF clustering. These insights into LLNM mechanisms in PTMC may contribute to future biomarker screening and the identification of therapeutic targets.

摘要

与无侧方淋巴结转移(LLNM)的患者相比,有LLNM的患者可能会经历更高的局部区域复发率和更差的预后,这凸显了进行有效的术前分层以可靠评估LLNM风险的必要性。在本研究中,我们从北京协和医院收集了甲状腺微小癌(PTMC)样本,并采用数据非依赖采集质谱蛋白质组学技术来鉴定有和无LLNM的PTMC组织中的蛋白质谱。结合癌症基因组图谱甲状腺癌进行了拟时间分析和单样本基因集富集分析,以进行功能协同分析并构建基于随机森林的预测模型。利用非负矩阵分解(NMF)聚类对PTMC的分子亚型进行分类。我们的研究结果表明,MAPK和PI3K等通路的差异激活对于增强PTMC的侧方淋巴结转移潜能至关重要。我们通过机器学习和公共数据库成功筛选出生物标志物,创建了一个有效的转移预测模型。此外,我们通过NMF聚类探索了与转移相关的PTMC亚型的机制。这些对PTMC中LLNM机制的见解可能有助于未来的生物标志物筛选和治疗靶点的鉴定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ece5/11705366/374d9d054dbe/pr4c00737_0001.jpg

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