Lima Tânia, Barros António S, Trindade Fábio, Ferreira Rita, Leite-Moreira Adelino, Barros-Silva Daniela, Jerónimo Carmen, Araújo Luís, Henrique Rui, Vitorino Rui, Fardilha Margarida
Department of Medical Sciences, Institute of Biomedicine-iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal.
Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (GEBC CI-IPOP) & Porto Comprehensive Cancer Center (P.CCC), 4200-072 Porto, Portugal.
Cancers (Basel). 2022 Apr 15;14(8):2001. doi: 10.3390/cancers14082001.
To identify new protein targets for PCa detection, first, a shotgun discovery experiment was performed to characterize the urinary proteome of PCa patients. This revealed 18 differentially abundant urinary proteins in PCa patients. Second, selected targets were clinically tested by immunoblot, and the soluble E-cadherin fragment was detected for the first time in the urine of PCa patients. Third, the proteogenome landscape of these PCa patients was characterized, revealing 1665 mutant protein isoforms. Statistical analysis revealed 6 differentially abundant mutant protein isoforms in PCa patients. Analysis of the likely effects of mutations on protein function and PPIs involving the dysregulated mutant protein isoforms suggests a protective role of mutations HSPG2Q1062H and VASNR161Q and an adverse role of AMBPA286G and CD55S162L in PCa patients. This work originally characterized the urinary proteome, focusing on the proteogenome profile of PCa patients, which is usually overlooked in the analysis of PCa and body fluids. Combined analysis of mass spectrometry data using two different software packages was performed for the first time in the context of PCa, which increased the robustness of the data analysis. The application of proteogenomics to urine proteomic analysis can be very enriching in mutation-related diseases such as cancer.
为了确定用于前列腺癌检测的新蛋白质靶点，首先进行了一项鸟枪法发现实验，以表征前列腺癌患者的尿液蛋白质组。这揭示了前列腺癌患者中有18种尿液蛋白质丰度存在差异。其次，通过免疫印迹对选定的靶点进行临床测试，首次在前列腺癌患者的尿液中检测到可溶性E-钙黏蛋白片段。第三，对这些前列腺癌患者的蛋白质基因组图谱进行了表征，揭示了1665种突变蛋白异构体。统计分析显示前列腺癌患者中有6种突变蛋白异构体丰度存在差异。对突变对蛋白质功能的可能影响以及涉及失调突变蛋白异构体的蛋白质-蛋白质相互作用的分析表明，突变HSPG2Q1062H和VASNR161Q在前列腺癌患者中具有保护作用，而AMBPA286G和CD55S162L具有不利作用。这项工作最初对尿液蛋白质组进行了表征，重点关注前列腺癌患者的蛋白质基因组图谱，这在前列腺癌和体液分析中通常被忽视。在前列腺癌的背景下，首次使用两个不同的软件包对质谱数据进行了联合分析，这提高了数据分析的稳健性。蛋白质基因组学在尿液蛋白质组分析中的应用对于癌症等与突变相关的疾病可能非常有意义。
