Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Departmen Unity of Chemistry, Biochemistry and Clinical Molecular Biology, Department of Diagnostic and Laboratory Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Int J Mol Sci. 2024 Aug 14;25(16):8830. doi: 10.3390/ijms25168830.
Tumor heterogeneity refers to the diversity observed among tumor cells: both between different tumors (inter-tumor heterogeneity) and within a single tumor (intra-tumor heterogeneity). These cells can display distinct morphological and phenotypic characteristics, including variations in cellular morphology, metastatic potential and variability treatment responses among patients. Therefore, a comprehensive understanding of such heterogeneity is necessary for deciphering tumor-specific mechanisms that may be diagnostically and therapeutically valuable. Innovative and multidisciplinary approaches are needed to understand this complex feature. In this context, proteogenomics has been emerging as a significant resource for integrating omics fields such as genomics and proteomics. By combining data obtained from both Next-Generation Sequencing (NGS) technologies and mass spectrometry (MS) analyses, proteogenomics aims to provide a comprehensive view of tumor heterogeneity. This approach reveals molecular alterations and phenotypic features related to tumor subtypes, potentially identifying therapeutic biomarkers. Many achievements have been made; however, despite continuous advances in proteogenomics-based methodologies, several challenges remain: in particular the limitations in sensitivity and specificity and the lack of optimal study models. This review highlights the impact of proteogenomics on characterizing tumor phenotypes, focusing on the critical challenges and current limitations of its use in different clinical and preclinical models for tumor phenotypic characterization.
包括不同肿瘤之间（肿瘤间异质性）和单个肿瘤内部（肿瘤内异质性）。这些细胞可以表现出不同的形态和表型特征，包括细胞形态、转移潜力和患者间治疗反应的可变性等方面的差异。因此，全面了解这种异质性对于破译可能具有诊断和治疗价值的肿瘤特异性机制是必要的。需要创新和多学科的方法来理解这一复杂特征。在这种背景下，蛋白质基因组学作为整合基因组学和蛋白质组学等组学领域的重要资源而崭露头角。通过将下一代测序（NGS）技术和质谱（MS）分析获得的数据相结合，蛋白质基因组学旨在提供肿瘤异质性的全面视图。这种方法揭示了与肿瘤亚型相关的分子改变和表型特征，可能有助于确定治疗生物标志物。已经取得了许多成就；然而，尽管基于蛋白质基因组学的方法学不断取得进展，但仍存在一些挑战：特别是敏感性和特异性的限制以及缺乏最佳的研究模型。本综述强调了蛋白质基因组学在描绘肿瘤表型方面的作用，重点介绍了其在不同临床和临床前肿瘤表型特征模型中的应用所面临的关键挑战和当前限制。
