Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, ENT Section, University of Pisa, Pisa, Italy.
Department of Pharmacy, University of Pisa, Pisa, Italy.
Head Neck Pathol. 2020 Jun;14(2):362-373. doi: 10.1007/s12105-019-01040-2. Epub 2019 May 16.
The purpose of this study was to define the proteome profile of fine needle aspiration (FNA) samples of malignant major salivary gland tumors (MSGT) compared to benign counterparts, and to evaluate potential clinical correlations and future applications. Patients affected by MSGT (n = 20), pleomorphic adenoma (PA) (n = 37) and Warthin's tumor (WT) (n = 14) were enrolled. Demographic, clinical and histopathological data were registered for all patients. FNA samples were processed to obtain the protein extracts. Protein separation was obtained by two-dimensional electrophoresis (2-DE) and proteins were identified by mass spectrometry. Western blot analysis was performed to validate the 2-DE results. Statistical differences between groups were calculated by the Mann-Whitney U test for non-normal data. Spearman's rank correlation coefficient was calculated to evaluate correlations among suggested protein biomarkers and clinical parameters. Twelve and 27 differentially expressed spots were found for MSGT versus PA and MSGT versus WT, respectively. Among these, annexin-5, cofilin-1, peptidyl-prolyl-cis-trans-isomerase-A and F-actin-capping-alpha-1 were able to differentiate MSGT from PA, WT, and healthy samples. Moreover, STRING analysis suggested cofilin-1 as a key node of protein interactions. Some of the overexpressed proteins are related to some clinical factors of our cohort, such as survival and outcome. Our results suggest potential protein biomarkers of MSGT, which could allow for more appropriate treatment plans, as well as shedding light on the molecular pathways involved.
本研究旨在定义恶性涎腺大唾液腺癌(MSGT)与良性涎腺肿瘤相比的细针抽吸(FNA)样本的蛋白质组谱,并评估其潜在的临床相关性和未来的应用。共纳入 20 例 MSGT 患者、37 例多形性腺瘤(PA)和 14 例沃辛瘤(WT)患者。对所有患者均记录了人口统计学、临床和组织病理学数据。FNA 样本用于获取蛋白质提取物。通过二维电泳(2-DE)获得蛋白质分离,通过质谱鉴定蛋白质。进行 Western blot 分析以验证 2-DE 结果。对于非正态数据,使用 Mann-Whitney U 检验计算组间的统计学差异。使用 Spearman 秩相关系数评估建议的蛋白质生物标志物与临床参数之间的相关性。MSGT 与 PA 相比有 12 个差异表达斑点,MSGT 与 WT 相比有 27 个差异表达斑点。其中,膜联蛋白-5、原肌球蛋白-1、肽基脯氨酰顺反异构酶-A 和 F-肌动蛋白帽-α-1 能够将 MSGT 与 PA、WT 和健康样本区分开来。此外,STRING 分析表明原肌球蛋白-1是蛋白质相互作用的关键节点。一些过表达的蛋白质与我们队列的一些临床因素有关,例如生存和预后。我们的结果表明 MSGT 的潜在蛋白质生物标志物,这可能允许制定更合适的治疗计划,并阐明所涉及的分子途径。