Proteomics profiling for the global and acetylated proteins of papillary thyroid cancers.

IF 2.1 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Proteome Science Pub Date : 2023-04-26 DOI:10.1186/s12953-023-00207-8
Wei Wei, Yuezhang Wu, Dong-Dong Chen, Yuntao Song, Guohui Xu, Qi Shi, Xiao-Ping Dong
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引用次数: 1

Abstract

Background: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy cancer among the malignancies of thyroid. Despite of wide usages of proteomics in PTC, the profile of acetylated proteins in PTC remains unsettled, which is helpful for understanding the carcinogenesis mechanism and identifying useful biomarkers for PTC.

Methods: The surgically removed specimens of cancer tissues (Ca-T) and adjacent normal tissues (Ca-N) from 10 female patients pathological diagnosed as PTC (TNM stage III) were enrolled in the study. After preparing the pooled extracts of the whole proteins and the acetylated proteins from 10 cases, TMT labeling and LC/MS/MS methods were applied to the assays of global proteomics and acetylated proteomics separately. Bioinformatics analysis, including KEGG, gene ontology (GO) and hierarchical clustering were performed. Some differentially expressed proteins (DEPs) and differentially expressed acetylated proteins (DEAPs) were validated by individual Western blots.

Results: Controlled with the normal tissues adjacent to the lesions, 147 out of 1923 identified proteins in tumor tissues were considered as DEPs in global proteomics, including 78 up-regulated and 69 down-regulated ones, while 57 out of 311 identified acetylated proteins in tumor tissues were DEAPs in acetylated proteomics, including 32 up-regulated and 25 down-regulated, respectively. The top 3 up- and down-regulated DEPs were fibronectin 1, KRT1B protein and chitinase-3-like protein 1, as well as keratin, type I cytoskeletal 16, A-gamma globin Osilo variant and Huntingtin interacting protein-1. The top 3 up- and down-regulated DEAPs were ribosomal protein L18a-like protein, alpha-1-acid glycoprotein 2 and eukaryotic peptide chain release factor GTP-binding subunit ERF3A, as well as trefoil factor 3, thyroglobulin and histone H2B. Functional GO annotation and KEGG pathway analysis based on the DEPs and DEAPs showed completely different changing pictures. Contrary to the top 10 up- and -down regulated DEPs, most of which were addressed in PTC and other types of carcinomas, changes of the majority DEAPs were not mentioned in the literatures.

Conclusions: Taken the profiling of the global and acetylated proteomics together will provide more broad view of protein alterations on the carcinogenesis and new direction for selecting biomarker for diagnosis of PTC.

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甲状腺乳头状癌的全蛋白和乙酰化蛋白蛋白质组学分析。
背景:甲状腺乳头状癌是甲状腺恶性肿瘤中最常见的内分泌恶性肿瘤。尽管蛋白质组学在PTC中的应用广泛,但PTC中乙酰化蛋白的谱仍然不确定,这有助于了解PTC的致癌机制和识别有用的生物标志物。方法:选取病理诊断为PTC (TNM III期)的10例女性患者手术切除的癌组织(Ca-T)及邻近正常组织(Ca-N)标本。将10例患者的全蛋白和乙酰化蛋白混合提取后,分别采用TMT标记法和LC/MS/MS法进行全蛋白组学和乙酰化蛋白组学分析。生物信息学分析包括KEGG、基因本体(GO)和分层聚类。一些差异表达蛋白(DEPs)和差异表达乙酰化蛋白(DEAPs)通过单独的Western blots验证。结果:以病变旁正常组织为对照,肿瘤组织中鉴定的1923个蛋白中147个为全局蛋白质组学deap,其中上调78个,下调69个;鉴定的肿瘤组织中311个乙酰化蛋白中57个为乙酰化蛋白质组学deap,其中上调32个,下调25个。前3位上调和下调的dep分别是纤维连接蛋白1、KRT1B蛋白和几丁质酶样蛋白1,以及角蛋白、I型细胞骨架16、a - γ珠蛋白Osilo变体和亨廷顿蛋白相互作用蛋白1。上调和下调前3位的deap分别是核糖体蛋白l18a样蛋白、α -1-酸性糖蛋白2和真核肽链释放因子gtp结合亚基ERF3A,以及三叶因子3、甲状腺球蛋白和组蛋白H2B。基于DEPs和DEAPs的功能性GO注释和KEGG通路分析显示了完全不同的变化图。与前10位上下调节的deap(其中大部分在PTC和其他类型的癌症中得到解决)相反,大多数deap的变化在文献中未被提及。结论:将全局蛋白质组学和乙酰化蛋白质组学结合起来,将为PTC的癌变过程提供更广阔的蛋白质改变视角,并为选择诊断PTC的生物标志物提供新的方向。
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来源期刊
Proteome Science
Proteome Science 生物-生化研究方法
CiteScore
2.90
自引率
0.00%
发文量
17
审稿时长
4.5 months
期刊介绍: Proteome Science is an open access journal publishing research in the area of systems studies. Proteome Science considers manuscripts based on all aspects of functional and structural proteomics, genomics, metabolomics, systems analysis and metabiome analysis. It encourages the submissions of studies that use large-scale or systems analysis of biomolecules in a cellular, organismal and/or environmental context. Studies that describe novel biological or clinical insights as well as methods-focused studies that describe novel methods for the large-scale study of any and all biomolecules in cells and tissues, such as mass spectrometry, protein and nucleic acid microarrays, genomics, next-generation sequencing and computational algorithms and methods are all within the scope of Proteome Science, as are electron topography, structural methods, proteogenomics, chemical proteomics, stem cell proteomics, organelle proteomics, plant and microbial proteomics. In spite of its name, Proteome Science considers all aspects of large-scale and systems studies because ultimately any mechanism that results in genomic and metabolomic changes will affect or be affected by the proteome. To reflect this intrinsic relationship of biological systems, Proteome Science will consider all such articles.
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