Wang Xi, Sun Jiameng, Feng Guodong, Tian Xu, Zhao Yang, Gao Zhiqiang, Sun Wei
Department of Otorhinolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.
Front Mol Neurosci. 2024 Aug 21;17:1391568. doi: 10.3389/fnmol.2024.1391568. eCollection 2024.
Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors that pose significant challenges in both diagnosis and treatment. The pathogenic mechanism remains unclear, and there is no proteomic analysis-based molecular classification. Therefore, gaining a deeper understanding of this disease from the protein level is crucial because proteins play a fundamental role in the occurrence and development of tumors.
We collected 44 tumor samples from patients diagnosed with HNPGL. The adrenal paraganglioma tissue ( = 46) was used as the disease control group and the chorda tympani nerves ( = 18) were used as the control group. High-pH reversed-phase liquid chromatography and liquid chromatography with tandem mass spectrometry analyses were used to build an integrated protein database of tumor samples. We then obtained two sets of differentially expressed proteins between the tumor group and the control group to identify the unique proteomic signatures of HNPGLs. Ingenuity pathway analysis annotations were used to perform the functional analysis. Subsequently, we developed a clinically relevant molecular classification for HNPGLs that connected the clinical characteristics with meaningful proteins and pathways to explain the varied clinical manifestations.
We identified 6,640 proteins in the HNPGL group, and 314 differentially expressed proteins unique to HNPGL were discovered via inter-group comparison. We identified two HNPGL subgroups that significantly differed in clinical manifestation and proteomic characteristics. On the basis of the proteomic results, we proposed a pathogenic mechanism underlying HNPGL.
We conducted a comprehensive analysis of the molecular mechanisms of HNPGL to build, for the first time, a clinically relevant molecular classification. By focusing on differential proteomic analyses between different types of paragangliomas, we were able to obtain a comprehensive description of the proteomic characteristics of HNPGL, which will be valuable for the search for significant biomarkers as a new treatment method for HNPGL.
头颈部副神经节瘤（HNPGLs）是罕见的神经内分泌肿瘤，在诊断和治疗方面都面临重大挑战。其致病机制尚不清楚，且缺乏基于蛋白质组学分析的分子分类。因此，从蛋白质水平更深入地了解这种疾病至关重要，因为蛋白质在肿瘤的发生和发展中起着基础性作用。
我们收集了44例被诊断为HNPGL的患者的肿瘤样本。将肾上腺副神经节瘤组织（n = 46）用作疾病对照组，将鼓索神经（n = 18）用作对照组。采用高pH反相液相色谱和液相色谱串联质谱分析来构建肿瘤样本的综合蛋白质数据库。然后，我们获得了肿瘤组与对照组之间两组差异表达蛋白，以识别HNPGLs独特的蛋白质组学特征。使用Ingenuity通路分析注释进行功能分析。随后，我们为HNPGLs开发了一种临床相关的分子分类，将临床特征与有意义的蛋白质和通路联系起来，以解释不同的临床表现。
我们在HNPGL组中鉴定出6640种蛋白质，通过组间比较发现了314种HNPGL特有的差异表达蛋白。我们鉴定出两个在临床表现和蛋白质组学特征上有显著差异的HNPGL亚组。基于蛋白质组学结果，我们提出了HNPGL的潜在致病机制。
我们对头颈部副神经节瘤的分子机制进行了全面分析，首次构建了临床相关的分子分类。通过专注于不同类型副神经节瘤之间的差异蛋白质组分析，我们能够对头颈部副神经节瘤的蛋白质组学特征进行全面描述，这对于寻找重要生物标志物作为头颈部副神经节瘤的新治疗方法具有重要价值。
