多形性腺瘤和癌外多形性腺瘤肿瘤发生:蛋白质组学分析。
Pleomorphic adenoma and carcinoma ex-pleomorphic adenoma tumorigenesis: A proteomic analysis.
发表日期:2024 Aug 18
作者:
Virgílio Gonzales Zanella, Sara Ferreira Dos Santos Costa, Lauren Frenzel Schuch, Emily Ferreira Salles Pilar, Adriana Franco Paes Leme, Jean Nunes Dos Santos, Syed Ali Khurram, Fatima Elalawy, Lynne Bingle, Fabio Daumas Nunes, Felipe Paiva Fonseca, Pablo Agustin Vargas, Manoela Domingues Martins, Vivian Petersen Wagner
来源:
ORAL DISEASES
摘要:
对正常唾液腺组织、多形性腺瘤 (PA) 和癌外多形性腺瘤 (CXPA) 进行全面的蛋白质组学分析,并使用免疫组织化学验证蛋白质组学结果。对 6 个正常唾液腺组织、7 个 PA 和 7 个 CXPA 样本进行激光分析显微切割,然后进行液相色谱与质谱联用。使用 MaxQuant 软件进行蛋白质鉴定和定量。分别使用Perseus平台和STRING工具进行统计分析和功能丰富。使用免疫组织化学进行验证。比较蛋白质组学分析显示三种组织类型中有 2680 种蛋白质,其中 799 种蛋白质在组间发生显着变化。与 PA 相比,易位蛋白 SEC63 同源物、膜联蛋白 A6 和 Biglycan 在 CXPA 中表达上调。与正常唾液腺相比,核心蛋白聚糖在 PA 和 CXPA 中均显着上调(log2 倍数变化分别为 7.58 和 7.38)。验证证实,与 PA 相比,CXPA 细胞外基质中双糖链蛋白聚糖和核心蛋白聚糖的水平升高。蛋白质组学分析确定了与 PA 恶性转化为 CXPA 相关的差异蛋白表达模式。研究结果表明,细胞外基质蛋白(特别是 Biglycan 和核心蛋白聚糖)在 PA 和 CXPA 的致瘤进展中发挥着至关重要的作用。© 2024 作者。约翰·威利出版的《口腔疾病》
To conduct a comprehensive proteomic analysis of normal salivary gland tissue, pleomorphic adenoma (PA), and carcinoma ex-pleomorphic adenoma (CXPA), and validate the proteomic findings using immunohistochemistry.Six normal salivary gland tissues, seven PA and seven CXPA samples underwent laser microdissection followed by liquid chromatography coupled to mass spectrometry. Protein identification and quantification were performed using MaxQuant software. Statistical analysis and functional enrichment were conducted using the Perseus platform and STRING tool, respectively. Immunohistochemistry was used for validation.Comparative proteomic analysis revealed 2680 proteins across the three tissue types, with 799 significantly altered between groups. Translocation protein SEC63 homolog, Annexin A6 and Biglycan were up-regulated in CXPA compared to PA. Decorin was markedly up-regulated in both PA and CXPA compared to normal salivary gland (log2 fold changes of 7.58 and 7.38, respectively). Validation confirmed elevated levels of Biglycan and Decorin in the extracellular matrix of CXPA compared to PA.Proteomic analysis identified differential protein expression patterns associated with malignant transformation of PA into CXPA. Findings indicate a crucial role for extracellular matrix proteins, specifically Biglycan and Decorin, in the tumorigenic progression of PA and CXPA.© 2024 The Author(s). Oral Diseases published by John Wiley & Sons Ltd.