Department Oncology and Hematology, The Second Hospital of Jilin University, Changchun, China.
Key Laboratory of Zoonosis Research, Ministry of Education, Jilin University, Changchun, China.
Biochim Biophys Acta Rev Cancer. 2022 Jul;1877(4):188735. doi: 10.1016/j.bbcan.2022.188735. Epub 2022 May 13.
Colorectal cancer (CRC) is one of the costliest health problems and ranks second in cancer-related mortality in developed countries. With the aid of proteomics, many protein biomarkers for the diagnosis, prognosis, and precise management of CRC have been identified. Furthermore, some protein biomarkers exhibit structural diversity after modifications. Post-translational modifications (PTMs), most of which are catalyzed by a variety of enzymes, extensively increase protein diversity and are involved in many complex and dynamic cellular processes through the regulation of protein function. Accumulating evidence suggests that abnormal PTM events are associated with a variety of human diseases, such as CRC, thus highlighting the need for studying PTMs to discover both the molecular mechanisms and therapeutic targets of CRC. In this review, we begin with a brief overview of the importance of protein PTMs, discuss the general strategies for proteomic profiling of several key PTMs (including phosphorylation, acetylation, glycosylation, ubiquitination, methylation, and citrullination), shift the emphasis to describing the specific methods used for delineating the global landscapes of each of these PTMs, and summarize the recent applications of these methods to explore the potential roles of the PTMs in CRC. Finally, we discuss the current status of PTM research on CRC and provide future perspectives on how PTM regulation can play an essential role in translational medicine for early diagnosis, prognosis stratification, and therapeutic intervention in CRC.
结直肠癌（CRC）是最昂贵的健康问题之一，在发达国家的癌症相关死亡率中排名第二。借助蛋白质组学，已经鉴定出许多用于 CRC 诊断、预后和精确管理的蛋白质生物标志物。此外，一些蛋白质生物标志物在修饰后表现出结构多样性。翻译后修饰（PTM），其中大部分由多种酶催化，通过调节蛋白质功能广泛增加蛋白质的多样性，并参与许多复杂和动态的细胞过程。越来越多的证据表明，异常的 PTM 事件与多种人类疾病有关，如 CRC，因此强调了研究 PTM 的必要性，以发现 CRC 的分子机制和治疗靶点。在这篇综述中，我们首先简要概述了蛋白质 PTM 的重要性，讨论了几种关键 PTM（包括磷酸化、乙酰化、糖基化、泛素化、甲基化和瓜氨酸化）的蛋白质组学分析的一般策略，重点描述了用于描绘这些 PTM 中的每一种的全局图谱的具体方法，并总结了这些方法在探索 PTM 在 CRC 中的潜在作用方面的最新应用。最后，我们讨论了 CRC 中 PTM 研究的现状，并提供了关于 PTM 调节如何在 CRC 的早期诊断、预后分层和治疗干预的转化医学中发挥重要作用的未来展望。
