PMID- 37845830 OWN - NLM STAT- MEDLINE DCOM- 20231228 LR - 20240417 IS - 1535-3699 (Electronic) IS - 1535-3702 (Print) IS - 1535-3699 (Linking) VI - 248 IP - 20 DP - 2023 Oct TI - Proteomics analysis of carotid body tumor revealed potential mechanisms and molecular differences among Shamblin classifications. PG - 1785-1798 LID - 10.1177/15353702231199475 [doi] AB - Carotid body tumors (CBTs) are a rare type of paraganglioma, and surgical resection is the only effective treatment. Because of the proximity of CBTs to the carotid artery, jugular vein, and cranial nerve, surgery is extremely difficult, with high risks of hemorrhage and neurovascular injury. The Shamblin classification is used for CBT clinical evaluation; however, molecular mechanisms underlying classification differences remain unclear. This study aimed to investigate pathogenic mechanisms and molecular differences between CBT types. In Shamblin I, II, and III tumors, differentially expressed proteins (DEPs) were identified using direct data-independent acquisition (DIA). DEPs were validated using immunohistochemistry. Proteomics profiling of three Shamblin subtypes differed significantly. Bioinformatics analysis showed that adrenomedullin signaling, protein kinase A signaling, vascular endothelial growth factor (VEGF) signaling, ephrin receptor signaling, gap junction signaling, interleukin (IL)-1 signaling, actin cytoskeleton signaling, endothelin-1 signaling, angiopoietin signaling, peroxisome proliferator-activated receptor (PPAR) signaling, bone morphogenetic protein (BMP) signaling, hypoxia-inducible factor 1-alpha (HIF-1alpha) signaling, and IL-6 signaling pathways were significantly enriched. Furthermore, 60 DEPs changed significantly with tumor progression. Immunohistochemistry validated several important DEPs, including aldehyde oxidase 1 (AOX1), mediator complex subunit 22 (MED22), carnitine palmitoyltransferase 1A (CPT1A), and heat shock transcription factor 1 (HSF1). To our knowledge, this is the first application of proteomics quantification in CBT. Our results will deepen the understanding of CBT-related pathogenesis and aid in identifying therapeutic targets for CBT treatment. FAU - Lv, Yanze AU - Lv Y AD - Department of Vascular Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. FAU - Gu, Guangchao AU - Gu G AD - Department of Vascular Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. FAU - Zeng, Rong AU - Zeng R AD - Department of Vascular Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. FAU - Liu, Zhili AU - Liu Z AD - Department of Vascular Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. FAU - Wu, Jianqiang AU - Wu J AUID- ORCID: 0000-0001-6773-9289 AD - Clinical Research Institute, National Science and Technology Key Infrastructure on Translational Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. FAU - Zheng, Yuehong AU - Zheng Y AUID- ORCID: 0000-0002-0704-5469 AD - Department of Vascular Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231016 PL - Switzerland TA - Exp Biol Med (Maywood) JT - Experimental biology and medicine (Maywood, N.J.) JID - 100973463 RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Humans MH - *Carotid Body Tumor/pathology/surgery MH - Proteomics MH - Vascular Endothelial Growth Factor A MH - Retrospective Studies MH - Carotid Arteries MH - Treatment Outcome PMC - PMC10792421 OTO - NOTNLM OT - Carotid body tumor OT - Shamblin classification OT - mass spectrometry OT - pathogenesis COIS- Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2023/10/17 06:42 MHDA- 2023/12/28 06:42 PMCR- 2024/04/16 CRDT- 2023/10/17 01:02 PHST- 2023/12/28 06:42 [medline] PHST- 2023/10/17 06:42 [pubmed] PHST- 2023/10/17 01:02 [entrez] PHST- 2024/04/16 00:00 [pmc-release] AID - 10.1177_15353702231199475 [pii] AID - 10.1177/15353702231199475 [doi] PST - ppublish SO - Exp Biol Med (Maywood). 2023 Oct;248(20):1785-1798. doi: 10.1177/15353702231199475. Epub 2023 Oct 16.