Integrated proteomic and phosphoproteomic analysis for characterization of colorectal cancer
Integrated proteomic and phosphoproteomic analysis for characterization of colorectal cancer
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用于表征结直肠癌的综合蛋白质组学和磷酸化蛋白质组学分析
DOI：
10.1016/j.jprot.2022.104808
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发表时间：
2023-01-20
影响因子：
3.3
通讯作者：
He，Guoyang
中科院分区：
文献类型：
--
作者：
Zhu，Huifang;Li，Yongzhen;He，Guoyang
蛋白质和磷酸化蛋白等翻译修饰蛋白在肿瘤发生中具有重要的调节作用。本研究试图阐明驱动结直肠癌（CRC）的失调蛋白。为了探索差异蛋白，我们对结直肠癌组织和邻近非癌组织进行了iTRAQ标记蛋白质组学和TMT标记磷酸化蛋白质组学分析。使用基因本体（GO）、京都基因与基因组百科全书（KEGG）和亚细胞定位分析分析定量蛋白的功能。根据结果，我们在结直肠癌中鉴定了330种差异蛋白和82种磷酸化蛋白。GO和KEGG分析表明，蛋白质变化主要与通过与其他分子结合来调节生物和代谢过程有关。蛋白质组学和磷酸化蛋白质组学分析的共表达关系显示，TMC5、SMC4、SLBP、VSIG2和NDRG2是显著失调的差异蛋白。此外，基于预测的共表达蛋白，我们发现茎环结合蛋白（SLBP）在CRC细胞中上调，并促进CRC的增殖和迁移。本研究报告了CRC的综合蛋白质组学和磷酸化蛋白质组学分析，以识别蛋白质改变对功能的影响，并提供CRC的候选诊断生物标志物或治疗靶点。意义将一种或多种高通量组学技术与生物信息学相结合，分析生物样品，探索生物分子及其功能之间的联系，可以为疾病机制研究提供更全面、多层次的见解。蛋白质组学、磷酸化蛋白质组学、代谢组学及其联合分析在结直肠癌的辅助诊断、发现生物标志物和新的治疗靶点方面发挥着重要作用。在这项综合蛋白质组学和磷蛋白质组学分析中，我们鉴定了结直肠癌组织中的蛋白质和磷蛋白，并分析了促进结直肠癌进展的潜在机制。本研究结果为进一步研究蛋白和磷酸化模式改变对结直肠癌预防和治疗的贡献奠定了基础。
Proteins and translationally modified proteins like phosphoproteins have essential regulatory roles in tumorigenesis. This study attempts to elucidate the dysregulated proteins driving colorectal cancer (CRC). To explore the differential proteins, we performed iTRAQ labeling proteomics and TMT labeling phosphoproteomics analysis of CRC tissues and adjacent non-cancerous tissues. The functions of quantified proteins were analyzed using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Subcellular localization analysis. Depending on the results, we identified 330 differential proteins and 82 phosphoproteins in CRC. GO and KEGG analyses demonstrated that protein changes were primarily associated with regulating biological and metabolic processes through binding to other molecules. Co-expression relationships between proteomic and phosphoproteomic analysis revealed that TMC5, SMC4, SLBP, VSIG2, and NDRG2 were significantly dysregulated differential proteins. Additionally, based on the predicted co-expression proteins, we identified that the stem-loop binding protein (SLBP) was up-regulated in CRC cells and promoted the proliferation and migration of CRC. This study reports an integrated proteomic and phosphoproteomic analysis of CRC to discern the functional impact of protein alterations and provides a candidate diagnostic biomarker or therapeutic target for CRC.SignificanceCombining one or more high-throughput omics technologies with bioinformatics to analyze biological samples and explore the links between biomolecules and their functions can provide more comprehensive and multi-level insights for disease mechanism research. Proteomics, phosphoproteomics, metabolomics and their combined analysis play an important role in the auxiliary diagnosis, the discovery of biomarkers and novel therapeutic targets for colorectal cancer. In this integrated proteomic and phosphoproteomic analysis, we identified proteins and phosphoproteins in colorectal cancer tissue and analyzed potential mechanisms contributing to progression in colorectal cancer. The results of this study provide a foundation to focus future experiments on the contribution of altered protein and phosphorylation patterns to prevention and treatment of colorectal cancer.