Clinical Proteomics Study Of Carotid Body Tumor

Objective:Carotid body tumors(CBTs)are a rare type of paraganglioma,with surgical resection as the only effective treatment.Because of their proximity 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 the clinical evaluation of CBTs;however,the molecular mechanisms underlying their differences remain unclear.The purpose of this study was to explore the pathogenic mechanisms and molecular differences between CBT types.Methods:Direct data-independent acquisition(DIA)-based proteomics was used to identify differentially expressed proteins(DEPs)in Shamblin Ⅰ,Ⅱ,and Ⅲ tumors.Immunohistochemistry was used to validate the DEPs.Results:Proteomics profiling of three Shamblin subtypes differed significantly.Bioinformatics analysis showed that adrenomedullin signaling pathway,gap-junction signaling,protein kinase A signaling,ephrin receptor signaling,IL-1 signaling,actin cytoskeleton signaling,VEGF signaling,endothelin-1 signaling,Angiopoietin signaling,PPAR signaling,BMP signaling pathway,HIF1α signaling,and IL-6 signaling pathways were significantly enriched.In addition,60 differentially expressed proteins(DEPs)changed significantly with tumor progression.Immunohistochemistry validated several important DEPs,including AOX1,MED22,CPT1 A,and HSF1.Conclusions: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 the treatment of CBT.Objective:Carotid body tumors are rare neoplasms located at the carotid bifurcation.Shamblin type Ⅲ lesions are characterized by aggressive invasion and a complex relationship with carotid vessels,for which surgical excision is required and associated with high incidence of neurovascular complications.Herein,the use of proteomics technology was investigated for identifying carotid body tumor targets to combine surgery with targeted treatment to reduce postoperative complications.Methods:This study included 12 patients with carotid body tumors(six type Ⅱ and six type Ⅲ).Protein array 440 was used to screen novel tissue-based biomarkers for Shamblin type Ⅱ/Ⅲ carotid body tunors.Proteins differentially expressed between the two groups were analyzed using bioinformatics and subjected to a customized array.Results:Fifteen targets were selected for validation using a customized array,and 12 biomarkers were consistent with those reported in previous studies.Conclusions:ENA-78 was found to be a promising biomarker or target to distinguish between type Ⅱ and Ⅲ carotid body tumors(area under the curve 0.950)or cure targets.Further,TARC,CD40,6ckine,Tie-2,MCSF,interleukin-15R,TRAIL-R3,leucine-rich repeats and immunoglobulin-like domain 3,Sonic hedgehog-N,and interleukin 2Rg represent a panel of promising diagnostic or adjuvant therapy targets for carotid body tumors.