Proteomic characterization of head and neck paraganglioma and its molecular classification

BackgroundHead 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 t...

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मुख्य लेखकों: Xi Wang, Jiameng Sun, Guodong Feng, Xu Tian, Yang Zhao, Zhiqiang Gao, Wei Sun
स्वरूप: लेख
भाषा:English
प्रकाशित: Frontiers Media S.A. 2024-08-01
श्रृंखला:Frontiers in Molecular Neuroscience
विषय:
ऑनलाइन पहुंच:https://www.frontiersin.org/articles/10.3389/fnmol.2024.1391568/full
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author Xi Wang
Jiameng Sun
Jiameng Sun
Guodong Feng
Xu Tian
Yang Zhao
Zhiqiang Gao
Wei Sun
author_facet Xi Wang
Jiameng Sun
Jiameng Sun
Guodong Feng
Xu Tian
Yang Zhao
Zhiqiang Gao
Wei Sun
author_sort Xi Wang
collection DOAJ
description BackgroundHead 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.MethodsWe collected 44 tumor samples from patients diagnosed with HNPGL. The adrenal paraganglioma tissue (N = 46) was used as the disease control group and the chorda tympani nerves (N = 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.ResultsWe 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.ConclusionWe 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.
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spelling doaj.art-f1dea2a6925c4717a0165d97a5ef0dd42024-08-21T06:01:37ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992024-08-011710.3389/fnmol.2024.13915681391568Proteomic characterization of head and neck paraganglioma and its molecular classificationXi Wang0Jiameng Sun1Jiameng Sun2Guodong Feng3Xu Tian4Yang Zhao5Zhiqiang Gao6Wei Sun7Department of Otorhinolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaDepartment of Otorhinolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Otorhinolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Otorhinolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Otorhinolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Basic Medical Sciences, School of Basic Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaBackgroundHead 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.MethodsWe collected 44 tumor samples from patients diagnosed with HNPGL. The adrenal paraganglioma tissue (N = 46) was used as the disease control group and the chorda tympani nerves (N = 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.ResultsWe 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.ConclusionWe 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.https://www.frontiersin.org/articles/10.3389/fnmol.2024.1391568/fullhead and neck paragangliomaproteomefunction annotationmolecular classificationpathogenic mechanism
spellingShingle Xi Wang
Jiameng Sun
Jiameng Sun
Guodong Feng
Xu Tian
Yang Zhao
Zhiqiang Gao
Wei Sun
Proteomic characterization of head and neck paraganglioma and its molecular classification
Frontiers in Molecular Neuroscience
head and neck paraganglioma
proteome
function annotation
molecular classification
pathogenic mechanism
title Proteomic characterization of head and neck paraganglioma and its molecular classification
title_full Proteomic characterization of head and neck paraganglioma and its molecular classification
title_fullStr Proteomic characterization of head and neck paraganglioma and its molecular classification
title_full_unstemmed Proteomic characterization of head and neck paraganglioma and its molecular classification
title_short Proteomic characterization of head and neck paraganglioma and its molecular classification
title_sort proteomic characterization of head and neck paraganglioma and its molecular classification
topic head and neck paraganglioma
proteome
function annotation
molecular classification
pathogenic mechanism
url https://www.frontiersin.org/articles/10.3389/fnmol.2024.1391568/full
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