Alterations of plasma exosomal proteins and motabolies are associated with the progression of castration-resistant prostate cancer
Abstract Background Current diagnosis tools for prostate cancer (PCa) such as serum PSA detection and prostate biopsy cannot distinguish dormant tumors from invasive malignancies, either be used as prognosis marker for castration resistant prostate cancer (CRPC), the lethal stage of PCa patients. Ex...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03860-3 |
| _version_ | 1797945728370212864 |
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| author | Pengyu Liu Wenxuan Wang Fei Wang Jiaqi Fan Jinan Guo Tao Wu Dongliang Lu Qingchun Zhou Zhuohao Liu Yuliang Wang Zhiqun Shang Franky Leung Chan Wei Yang Xin Li Shan-Chao Zhao Qingyou Zheng Fei Wang Dinglan Wu |
| author_facet | Pengyu Liu Wenxuan Wang Fei Wang Jiaqi Fan Jinan Guo Tao Wu Dongliang Lu Qingchun Zhou Zhuohao Liu Yuliang Wang Zhiqun Shang Franky Leung Chan Wei Yang Xin Li Shan-Chao Zhao Qingyou Zheng Fei Wang Dinglan Wu |
| author_sort | Pengyu Liu |
| collection | DOAJ |
| description | Abstract Background Current diagnosis tools for prostate cancer (PCa) such as serum PSA detection and prostate biopsy cannot distinguish dormant tumors from invasive malignancies, either be used as prognosis marker for castration resistant prostate cancer (CRPC), the lethal stage of PCa patients. Exosomes have been widely investigated as promising biomarkers for various diseases. We aim to characterize the proteomic and metabolomic profile of exosomes and to evaluate their potential value for the diagnosis of PCa, especially CRPC. We also investigate the functions of some specific exosome biomarkers in the progression of CRPC. Methods Integrated proteomics and metabolomics analysis were performed for plasma-derived exosomes collected from tumor-free controls (TFC), PCa and CRPC patients. Expression of specific exosomal proteins were further validated by targeted 4D-parallel reaction monitoring (PRM) mass spectrometry among the three cohorts. Tissue distribution and functional role of exosomal protein LRG1 was studied in clinical PCa tissue samples and cell line models. Results Three potential exosomal protein markers were identified. The apolipoprotein E level in PCa samples was 1.7-fold higher than that in TFC (receiver operating characteristic value, 0.74). Similarly, the levels of exosome-derived leucine-rich alpha2-glycoprotein 1 (LRG1) and inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) in the CRPC group were 1.7 and 2.04 times, respectively, higher than those in the PCa group (ROC values, 0.84 and 0.85, respectively), indicating that LRG1 and ITIH3 could serve as predictive markers for CRPC. For metabolomic evaluation of exosomes, a series of differentially expressed metabolites were identified, and a combined metabolite panel showed ROC value of 0.94 for distinguishing PCa from TFC and 0.97 for distinguishing CRPC from PCa. Immunohistochemistry of tissue microarray showed that LRG1 protein was significantly upregulated in advanced prostate cancer and functional assay revealed that ectopic expression of LRG1 can significantly enhance the malignant phenotype of prostate cancer cells. More importantly, PCa cell derived LRG1-overexpressed exosomes remarkably promoted angiogenesis. Conclusion Integration of proteomics and metabolomics data generated proteomic and metabolic signatures of plasma exosomes that may facilitate discrimination of CRPC from PCa and TFC patients, suggesting the potential of exosomal proteins and metabolites as CRPC markers. The study also confirmed the important role of exosomal protein LRG1 in PCa malignant progression. |
| first_indexed | 2024-04-10T20:59:42Z |
| format | Article |
| id | doaj.art-3e2d51a099714636a4652fe7f83125d7 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-10T20:59:42Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-3e2d51a099714636a4652fe7f83125d72023-01-22T12:23:26ZengBMCJournal of Translational Medicine1479-58762023-01-0121112010.1186/s12967-022-03860-3Alterations of plasma exosomal proteins and motabolies are associated with the progression of castration-resistant prostate cancerPengyu Liu0Wenxuan Wang1Fei Wang2Jiaqi Fan3Jinan Guo4Tao Wu5Dongliang Lu6Qingchun Zhou7Zhuohao Liu8Yuliang Wang9Zhiqun Shang10Franky Leung Chan11Wei Yang12Xin Li13Shan-Chao Zhao14Qingyou Zheng15Fei Wang16Dinglan Wu17Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical UniversityDepartment of Urology, Guangdong Hospital of Traditional Chinese MedicineShenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical UniversityShenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical UniversityDepartment of Urology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology)Department of Urology, Shenzhen Hospital, Southern Medical UniversityDepartment of Urology, Shenzhen Hospital, Southern Medical UniversityDepartment of Urology, Shenzhen Hospital, Southern Medical UniversityShenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical UniversityShenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical UniversityDepartment of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical UniversitySchool of Biomedical Sciences, The Chinese University of Hong KongDepartment of Pathology, School of Basic Medical Sciences, Southern Medical UniversityShenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical UniversityDepartment of Urology, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Urology, Shenzhen Hospital, Southern Medical UniversityDepartment of Urology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical UniversityShenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical UniversityAbstract Background Current diagnosis tools for prostate cancer (PCa) such as serum PSA detection and prostate biopsy cannot distinguish dormant tumors from invasive malignancies, either be used as prognosis marker for castration resistant prostate cancer (CRPC), the lethal stage of PCa patients. Exosomes have been widely investigated as promising biomarkers for various diseases. We aim to characterize the proteomic and metabolomic profile of exosomes and to evaluate their potential value for the diagnosis of PCa, especially CRPC. We also investigate the functions of some specific exosome biomarkers in the progression of CRPC. Methods Integrated proteomics and metabolomics analysis were performed for plasma-derived exosomes collected from tumor-free controls (TFC), PCa and CRPC patients. Expression of specific exosomal proteins were further validated by targeted 4D-parallel reaction monitoring (PRM) mass spectrometry among the three cohorts. Tissue distribution and functional role of exosomal protein LRG1 was studied in clinical PCa tissue samples and cell line models. Results Three potential exosomal protein markers were identified. The apolipoprotein E level in PCa samples was 1.7-fold higher than that in TFC (receiver operating characteristic value, 0.74). Similarly, the levels of exosome-derived leucine-rich alpha2-glycoprotein 1 (LRG1) and inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) in the CRPC group were 1.7 and 2.04 times, respectively, higher than those in the PCa group (ROC values, 0.84 and 0.85, respectively), indicating that LRG1 and ITIH3 could serve as predictive markers for CRPC. For metabolomic evaluation of exosomes, a series of differentially expressed metabolites were identified, and a combined metabolite panel showed ROC value of 0.94 for distinguishing PCa from TFC and 0.97 for distinguishing CRPC from PCa. Immunohistochemistry of tissue microarray showed that LRG1 protein was significantly upregulated in advanced prostate cancer and functional assay revealed that ectopic expression of LRG1 can significantly enhance the malignant phenotype of prostate cancer cells. More importantly, PCa cell derived LRG1-overexpressed exosomes remarkably promoted angiogenesis. Conclusion Integration of proteomics and metabolomics data generated proteomic and metabolic signatures of plasma exosomes that may facilitate discrimination of CRPC from PCa and TFC patients, suggesting the potential of exosomal proteins and metabolites as CRPC markers. The study also confirmed the important role of exosomal protein LRG1 in PCa malignant progression.https://doi.org/10.1186/s12967-022-03860-3PCaCRPCExosomesProteomicsMetabolomicsBiomarkers |
| spellingShingle | Pengyu Liu Wenxuan Wang Fei Wang Jiaqi Fan Jinan Guo Tao Wu Dongliang Lu Qingchun Zhou Zhuohao Liu Yuliang Wang Zhiqun Shang Franky Leung Chan Wei Yang Xin Li Shan-Chao Zhao Qingyou Zheng Fei Wang Dinglan Wu Alterations of plasma exosomal proteins and motabolies are associated with the progression of castration-resistant prostate cancer Journal of Translational Medicine PCa CRPC Exosomes Proteomics Metabolomics Biomarkers |
| title | Alterations of plasma exosomal proteins and motabolies are associated with the progression of castration-resistant prostate cancer |
| title_full | Alterations of plasma exosomal proteins and motabolies are associated with the progression of castration-resistant prostate cancer |
| title_fullStr | Alterations of plasma exosomal proteins and motabolies are associated with the progression of castration-resistant prostate cancer |
| title_full_unstemmed | Alterations of plasma exosomal proteins and motabolies are associated with the progression of castration-resistant prostate cancer |
| title_short | Alterations of plasma exosomal proteins and motabolies are associated with the progression of castration-resistant prostate cancer |
| title_sort | alterations of plasma exosomal proteins and motabolies are associated with the progression of castration resistant prostate cancer |
| topic | PCa CRPC Exosomes Proteomics Metabolomics Biomarkers |
| url | https://doi.org/10.1186/s12967-022-03860-3 |
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