Abstract：
Sinonasal undifferentiated carcinoma (SNUC) is a highly malignant tumor in the nasal cavity or paranasal sinuses. Morphoproteomics has defined its biology to some degree, allowing the identification of targeted therapeutic options with clinical efficacy [1]. This study\'s objective was to identify putative SNUC pathways that are known to pose a block in differentiation both in early embryogenesis and in tumorigenesis or that might promote metastasis and recurrent disease.
METHODS: Morphoproteomic analysis of SNUC from a case study of this patient included immunohistochemical probes to detect c-Myc, EZH2, Sirt1 and CXCR4 protein analytes. Biomedical analytics schematically showed the interactions of these analytes with the morphoproteomic findings and illustrated targeted therapeutic options.
RESULTS: Representative sections of this patient\'s tumor displayed plasmalemmal expression for CXCR4 and nuclear immunopositivity for c-Myc, EZH2, and Sirt1. This coincided with their block in differentiation and their proliferative state with progression into the mitotic phase. Biomedical analytics integrated the morphoproteomic findings with the undifferentiated and proliferative state of SNUC and depicted pharmacogenomic and other related factors that target the c-Myc, EZH2, Sirt1 and CXCR4 pathways.
CONCLUSIONS: Morphoproteomics and biomedical analytics have identified c-Myc, EZH2, Sirt1 and CXCR4 pathways that collectively could contribute to the block in differentiation and increase the propensity for recurrence and metastasis in SNUC. This suggests that combinatorial therapies modulating these pathways could be used in a maintenance mode to minimize the risk of recurrent disease.
METHODS: Morphoproteomic analysis of SNUC from a case study of this patient included immunohistochemical probes to detect c-Myc, EZH2, Sirt1 and CXCR4 protein analytes. Biomedical analytics schematically showed the interactions of these analytes with the morphoproteomic findings and illustrated targeted therapeutic options.
RESULTS: Representative sections of this patient\'s tumor displayed plasmalemmal expression for CXCR4 and nuclear immunopositivity for c-Myc, EZH2, and Sirt1. This coincided with their block in differentiation and their proliferative state with progression into the mitotic phase. Biomedical analytics integrated the morphoproteomic findings with the undifferentiated and proliferative state of SNUC and depicted pharmacogenomic and other related factors that target the c-Myc, EZH2, Sirt1 and CXCR4 pathways.
CONCLUSIONS: Morphoproteomics and biomedical analytics have identified c-Myc, EZH2, Sirt1 and CXCR4 pathways that collectively could contribute to the block in differentiation and increase the propensity for recurrence and metastasis in SNUC. This suggests that combinatorial therapies modulating these pathways could be used in a maintenance mode to minimize the risk of recurrent disease.
摘要：
鼻窦未分化癌（SNUC）是鼻腔或鼻旁窦的高度恶性肿瘤。形态蛋白质组学在一定程度上定义了它的生物学，允许确定具有临床疗效的靶向治疗选择[1]。本研究的目的是鉴定假定的SNUC途径，已知这些途径在早期胚胎发生和肿瘤发生中都会阻碍分化，或者可能促进转移和复发性疾病。
方法：来自该患者的病例研究的SNUC的形态蛋白质组学分析包括检测c-Myc的免疫组织化学探针，EZH2、Sirt1和CXCR4蛋白分析物。生物医学分析示意性地显示了这些分析物与形态蛋白质组学发现的相互作用，并说明了靶向治疗选择。
结果：该患者肿瘤的代表性部分显示CXCR4的质膜表达和c-Myc的核免疫阳性，EZH2和Sirt1。这与它们的分化阻滞和进入有丝分裂期的增殖状态相吻合。生物医学分析将形态蛋白质组学发现与SNUC的未分化和增殖状态相结合，并描述了靶向c-Myc的药物基因组和其他相关因素，EZH2、Sirt1和CXCR4通路。
结论：形态蛋白质组学和生物医学分析已经确定了c-Myc，EZH2，Sirt1和CXCR4途径共同可能导致分化阻滞并增加SNUC中复发和转移的倾向。这表明调节这些途径的组合疗法可以用于维持模式以最小化疾病复发的风险。
方法：来自该患者的病例研究的SNUC的形态蛋白质组学分析包括检测c-Myc的免疫组织化学探针，EZH2、Sirt1和CXCR4蛋白分析物。生物医学分析示意性地显示了这些分析物与形态蛋白质组学发现的相互作用，并说明了靶向治疗选择。
结果：该患者肿瘤的代表性部分显示CXCR4的质膜表达和c-Myc的核免疫阳性，EZH2和Sirt1。这与它们的分化阻滞和进入有丝分裂期的增殖状态相吻合。生物医学分析将形态蛋白质组学发现与SNUC的未分化和增殖状态相结合，并描述了靶向c-Myc的药物基因组和其他相关因素，EZH2、Sirt1和CXCR4通路。
结论：形态蛋白质组学和生物医学分析已经确定了c-Myc，EZH2，Sirt1和CXCR4途径共同可能导致分化阻滞并增加SNUC中复发和转移的倾向。这表明调节这些途径的组合疗法可以用于维持模式以最小化疾病复发的风险。
