A Pilot Study of Exosome Proteomic Profiling Reveals Dysregulated Metabolic Pathways in Endometrial Cancer
<b>Background/Objectives</b>: Endometrial cancer (EC) is the second most frequent gynecological malignant tumor in postmenopausal women. Pathogenic mechanisms related to the onset and development of the disease are still unknown. To identify dysregulated proteins associated with EC we ex...
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2025-01-01
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| author | Feras Kharrat Valeria Capaci Andrea Conti Valentina Golino Pietro Campiglia Nour Balasan Michelangelo Aloisio Danilo Licastro Lorenzo Monasta Federica Caponneto Antonio Paolo Beltrami Federico Romano Giovanni di Lorenzo Giuseppe Ricci Blendi Ura |
| author_facet | Feras Kharrat Valeria Capaci Andrea Conti Valentina Golino Pietro Campiglia Nour Balasan Michelangelo Aloisio Danilo Licastro Lorenzo Monasta Federica Caponneto Antonio Paolo Beltrami Federico Romano Giovanni di Lorenzo Giuseppe Ricci Blendi Ura |
| author_sort | Feras Kharrat |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Endometrial cancer (EC) is the second most frequent gynecological malignant tumor in postmenopausal women. Pathogenic mechanisms related to the onset and development of the disease are still unknown. To identify dysregulated proteins associated with EC we exploited a combined in vitro/in silico approach analyzing the proteome of exosomes with advanced MS techniques and annotating their results by using Chymeris1 AI tools. <b>Methods</b>: To this aim in this pilot study, we performed a deep proteomics analysis with high resolution MS (HRMS), advanced computational tools and western blotting for proteomics data validation. <b>Results</b>: That allowed us to identify 3628 proteins in serum albumin-depleted exosomes from 10 patients with EC compared to 10 healthy controls. This is the largest number of proteins identified in EC serum EVs. After quantification and statistical analysis, we identified 373 significantly (<i>p</i> < 0.05) dysregulated proteins involved in neutrophil and platelet degranulation pathways. A more detailed bioinformatics analysis revealed 61 dysregulated enzymes related to metabolic and catabolic pathways linked to tumor invasion. Through this analysis, we identified 49 metabolic and catabolic pathways related to tumor growth. <b>Conclusions</b>: Altogether, data shed light on the metabolic pathways involved in tumors. This is very important for understanding the metabolism of EC and for the development of new therapies. |
| format | Article |
| id | doaj-art-a4e137a63c634c61b6a29cc8b8667e48 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| series | Biomedicines |
| spelling | doaj-art-a4e137a63c634c61b6a29cc8b8667e482025-01-24T13:23:59ZengMDPI AGBiomedicines2227-90592025-01-011319510.3390/biomedicines13010095A Pilot Study of Exosome Proteomic Profiling Reveals Dysregulated Metabolic Pathways in Endometrial CancerFeras Kharrat0Valeria Capaci1Andrea Conti2Valentina Golino3Pietro Campiglia4Nour Balasan5Michelangelo Aloisio6Danilo Licastro7Lorenzo Monasta8Federica Caponneto9Antonio Paolo Beltrami10Federico Romano11Giovanni di Lorenzo12Giuseppe Ricci13Blendi Ura14Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 65/1 Via dell’Istria, 34137 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 65/1 Via dell’Istria, 34137 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 65/1 Via dell’Istria, 34137 Trieste, ItalyDepartment of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Salerno, ItalyDepartment of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Salerno, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 65/1 Via dell’Istria, 34137 Trieste, ItalyFunctional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology-IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, ItalyAREA Science Park, 34149 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 65/1 Via dell’Istria, 34137 Trieste, ItalyDepartment of Medicine, University of Udine, 33100 Udine, ItalyDepartment of Medicine, University of Udine, 33100 Udine, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 65/1 Via dell’Istria, 34137 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 65/1 Via dell’Istria, 34137 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 65/1 Via dell’Istria, 34137 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 65/1 Via dell’Istria, 34137 Trieste, Italy<b>Background/Objectives</b>: Endometrial cancer (EC) is the second most frequent gynecological malignant tumor in postmenopausal women. Pathogenic mechanisms related to the onset and development of the disease are still unknown. To identify dysregulated proteins associated with EC we exploited a combined in vitro/in silico approach analyzing the proteome of exosomes with advanced MS techniques and annotating their results by using Chymeris1 AI tools. <b>Methods</b>: To this aim in this pilot study, we performed a deep proteomics analysis with high resolution MS (HRMS), advanced computational tools and western blotting for proteomics data validation. <b>Results</b>: That allowed us to identify 3628 proteins in serum albumin-depleted exosomes from 10 patients with EC compared to 10 healthy controls. This is the largest number of proteins identified in EC serum EVs. After quantification and statistical analysis, we identified 373 significantly (<i>p</i> < 0.05) dysregulated proteins involved in neutrophil and platelet degranulation pathways. A more detailed bioinformatics analysis revealed 61 dysregulated enzymes related to metabolic and catabolic pathways linked to tumor invasion. Through this analysis, we identified 49 metabolic and catabolic pathways related to tumor growth. <b>Conclusions</b>: Altogether, data shed light on the metabolic pathways involved in tumors. This is very important for understanding the metabolism of EC and for the development of new therapies.https://www.mdpi.com/2227-9059/13/1/95proteomicsmass spectrometryexosomes |
| spellingShingle | Feras Kharrat Valeria Capaci Andrea Conti Valentina Golino Pietro Campiglia Nour Balasan Michelangelo Aloisio Danilo Licastro Lorenzo Monasta Federica Caponneto Antonio Paolo Beltrami Federico Romano Giovanni di Lorenzo Giuseppe Ricci Blendi Ura A Pilot Study of Exosome Proteomic Profiling Reveals Dysregulated Metabolic Pathways in Endometrial Cancer Biomedicines proteomics mass spectrometry exosomes |
| title | A Pilot Study of Exosome Proteomic Profiling Reveals Dysregulated Metabolic Pathways in Endometrial Cancer |
| title_full | A Pilot Study of Exosome Proteomic Profiling Reveals Dysregulated Metabolic Pathways in Endometrial Cancer |
| title_fullStr | A Pilot Study of Exosome Proteomic Profiling Reveals Dysregulated Metabolic Pathways in Endometrial Cancer |
| title_full_unstemmed | A Pilot Study of Exosome Proteomic Profiling Reveals Dysregulated Metabolic Pathways in Endometrial Cancer |
| title_short | A Pilot Study of Exosome Proteomic Profiling Reveals Dysregulated Metabolic Pathways in Endometrial Cancer |
| title_sort | pilot study of exosome proteomic profiling reveals dysregulated metabolic pathways in endometrial cancer |
| topic | proteomics mass spectrometry exosomes |
| url | https://www.mdpi.com/2227-9059/13/1/95 |
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