卵巢粒层细胞瘤与纤维卵泡膜细胞瘤蛋白质组学研究OACSTPCD

Objective:Ovary granulosa cell tumor(OGCT)and ovarian fibrothecoma(OF)are relatively common types of ovarian sex cord-stromal tumors.Both contain follicular membrane cells,and when OGCT exhibits a diffuse growth pattern,it shares similarities in histological morphology with cell-rich OF and luteinized OF,causing difficulty in pathological diagnosis.This study aims to explore the proteomic differences,and screen for differentially expressed proteins(DEPs)between them,and find biomarkers for distinguishing between the OGCT and OF. Methods:Fresh tumor tissue samples from 5 patients with OGCT and 5 patients with OF were selected.Protein quantification was performed using protein digestion,peptide purification,and liquid chromatography-mass spectrometry/mass spectrometry analysis(LC-MS/MS).Software was used to analyze DEPs in OGCT and OF proteins.The gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on DEPs,and functional annotations of proteins/genes were conducted in terms of biological processes(BP),molecular function(MF),and cell component(CC)to explore the signaling pathways significantly enriched by DEPs.Interaction information of selected DEPs was obtained from the search tool for the retrieval of interacting genes/proteins(STRING)database to construct a protein-protein interaction(PPI)network.Tissue chip technology and immunohistochemical staining were used to verify the expression of selected DEPs in OGCT and OF in 26 OGCT and 28 OF paraffin-embedded tissues. Results:A total of 24 significantly DEPs between OGCT and OF were identified,with 13 proteins up-regulated in OGCT and 11 proteins up-regulated in OF.GO enrichment analysis showed that pathways enriched in BP included extracellular matrix(ECM)organization processes,extracellular structural organization,organic acid,carboxylic acid,fatty acid,and monocarboxylic acid catabolic processes.Pathways enriched in CC included ECM containing collagen,endoplasmic reticulum lumen,and mitochondrial matrix.Pathways enriched in MF included sulfide compound binding,ECM structural constituents,amide binding,collagen binding,transferase activity,and acyltransferase.KEGG enrichment analysis showed that upregulated DEPs were mainly enriched in valine,leucine,and isoleucine degradation pathways,while downregulated DEPs were mainly enriched in defects in congenital glutathione metabolism,deficiency,prion disease,arachidonic acid metabolic pathway,complement system,cytochrome P450 metabolism on heterogeneic organisms,and drug metabolism-cytochrome P450.PPI results showed interactions among the 24 DEPs and multiple proteins immunohistochemical staining of tissue chips showed that PLOD3 was highly expressed in OGCT and low in OF,consistent with the enrichment analysis results. Conclusion:Through proteomic technology and bioinformatics analysis methods,a total of 24 DEPs are selected,and through immunohistochemical validation,the detection of PLOD3 has potential clinical value in distinguishing between OGCT and OF,and it is expected to become a biological marker for the differential diagnosis of OGCT and OF.