Plasma Proteomics and Metabolomics of Aromatase Inhibitors-Related Musculoskeletal Syndrome in Early Breast Cancer Patients
Background: Aromatase inhibitors-related musculoskeletal syndrome (AIMSS) is a common side effect experienced by early breast cancer patients undergoing endocrine therapy. This condition can result in medication discontinuation and a diminished quality of life. The objective of this study was to cha...
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2025-02-01
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| author | Feng Jing Lingyun Jiang Yuling Cao Maoting Tian Jiajia Qiu Jing Zhang Lichen Tang Renquan Lu Yan Hu |
| author_facet | Feng Jing Lingyun Jiang Yuling Cao Maoting Tian Jiajia Qiu Jing Zhang Lichen Tang Renquan Lu Yan Hu |
| author_sort | Feng Jing |
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| description | Background: Aromatase inhibitors-related musculoskeletal syndrome (AIMSS) is a common side effect experienced by early breast cancer patients undergoing endocrine therapy. This condition can result in medication discontinuation and a diminished quality of life. The objective of this study was to characterize AIMSS, investigate its pathogenesis, and identify potential biomarkers at both the protein and metabolic levels. Methods: We collected peripheral blood samples from 60 women diagnosed with breast cancer undergoing aromatase inhibitor therapy, of whom 30 had AIMSS and 30 did not. The samples were analyzed using four-dimensional data-independent acquisition (DIA)-based proteomics and untargeted metabolomics, employing liquid chromatography–mass spectrometry (LC–MS) on the latest platform. Results: The mean age of participants was 49.2 (11.3) years in the AIMSS group and 50.1 (11.5) years in the non-AIMSS group. There were no statistically significant differences between the two groups in terms of age, BMI, education level, clinical stage, and treatment. In total, we identified 3473 proteins and 1247 metabolites in the samples. The chemokine signaling pathway (<i>p</i> = 0.015), cytokine–cytokine receptor interaction (<i>p</i> = 0.015), complement and coagulation cascades (<i>p</i> = 0.004), neuroactive ligand–receptor interaction (<i>p</i> = 0.004), and the estrogen signaling pathway (<i>p</i> = 0.004) were significant enriched in differentially expressed proteins (DEPs). GnRH secretion (<i>p</i> < 0.001), sphingolipid signaling pathways (<i>p</i> < 0.001), endocrine resistance (<i>p</i> < 0.001), the estrogen signaling pathway (<i>p</i> = 0.001), endocrine and other factor-regulated calcium reabsorption (<i>p</i> = 0.001), dopaminergic synapse (<i>p</i> = 0.003), regulation of lipolysis in adipocytes (<i>p</i> = 0.004), biosynthesis of cofactors (<i>p</i> = 0.004), thyroid hormone synthesis (<i>p</i> = 0.008), aldosterone synthesis and secretion (<i>p</i> = 0.001), taurine and hypotaurine metabolism (<i>p</i> = 0.011), ovarian steroidogenesis (<i>p</i> = 0.011), and the cAMP signaling pathway (<i>p</i> = 0.011) were significantly enriched in differentially expressed metabolites (DEMs). Complement C3 (<i>p</i> = 0.004), platelet factor 4 (<i>p</i> = 0.015), KRT10 (<i>p</i> = 0.004), KRT14 (<i>p</i> = 0.004), beta-estradiol (<i>p</i> = 0.019), testosterone (<i>p</i> = 0.023), sphingosine (<i>p</i> < 0.001), and 1-stearoyl-2-arachidonoyl-sn-glycerol (<i>p</i> = 0.039) could be the monitoring and therapeutic targets for AIMSS. Conclusions: This study offered new insights into the mechanisms underlying musculoskeletal symptoms associated with aromatase inhibitors. It also highlighted potential biomarkers for predicting and addressing these symptoms in breast cancer patients, paving the way for improved intervention strategies. |
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| issn | 2218-1989 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-4a036f70cac540fdb0ea667f09a0b4572025-08-20T01:48:48ZengMDPI AGMetabolites2218-19892025-02-0115315310.3390/metabo15030153Plasma Proteomics and Metabolomics of Aromatase Inhibitors-Related Musculoskeletal Syndrome in Early Breast Cancer PatientsFeng Jing0Lingyun Jiang1Yuling Cao2Maoting Tian3Jiajia Qiu4Jing Zhang5Lichen Tang6Renquan Lu7Yan Hu8School of Nursing, Fudan University and Fudan University Centre for Evidence-Based Nursing: A Joanna Briggs Institute Centre of Excellence, Shanghai 200032, ChinaSchool of Nursing, Fudan University and Fudan University Centre for Evidence-Based Nursing: A Joanna Briggs Institute Centre of Excellence, Shanghai 200032, ChinaSchool of Nursing, Fudan University and Fudan University Centre for Evidence-Based Nursing: A Joanna Briggs Institute Centre of Excellence, Shanghai 200032, ChinaSchool of Nursing, Fudan University and Fudan University Centre for Evidence-Based Nursing: A Joanna Briggs Institute Centre of Excellence, Shanghai 200032, ChinaDepartment of Nursing Administration, Shanghai Cancer Center, Fudan University, Shanghai 200032, ChinaDepartment of Clinical Laboratory, Shanghai Cancer Center, Fudan University, Shanghai 200032, ChinaDepartment of Breast Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, ChinaDepartment of Clinical Laboratory, Shanghai Cancer Center, Fudan University, Shanghai 200032, ChinaSchool of Nursing, Fudan University and Fudan University Centre for Evidence-Based Nursing: A Joanna Briggs Institute Centre of Excellence, Shanghai 200032, ChinaBackground: Aromatase inhibitors-related musculoskeletal syndrome (AIMSS) is a common side effect experienced by early breast cancer patients undergoing endocrine therapy. This condition can result in medication discontinuation and a diminished quality of life. The objective of this study was to characterize AIMSS, investigate its pathogenesis, and identify potential biomarkers at both the protein and metabolic levels. Methods: We collected peripheral blood samples from 60 women diagnosed with breast cancer undergoing aromatase inhibitor therapy, of whom 30 had AIMSS and 30 did not. The samples were analyzed using four-dimensional data-independent acquisition (DIA)-based proteomics and untargeted metabolomics, employing liquid chromatography–mass spectrometry (LC–MS) on the latest platform. Results: The mean age of participants was 49.2 (11.3) years in the AIMSS group and 50.1 (11.5) years in the non-AIMSS group. There were no statistically significant differences between the two groups in terms of age, BMI, education level, clinical stage, and treatment. In total, we identified 3473 proteins and 1247 metabolites in the samples. The chemokine signaling pathway (<i>p</i> = 0.015), cytokine–cytokine receptor interaction (<i>p</i> = 0.015), complement and coagulation cascades (<i>p</i> = 0.004), neuroactive ligand–receptor interaction (<i>p</i> = 0.004), and the estrogen signaling pathway (<i>p</i> = 0.004) were significant enriched in differentially expressed proteins (DEPs). GnRH secretion (<i>p</i> < 0.001), sphingolipid signaling pathways (<i>p</i> < 0.001), endocrine resistance (<i>p</i> < 0.001), the estrogen signaling pathway (<i>p</i> = 0.001), endocrine and other factor-regulated calcium reabsorption (<i>p</i> = 0.001), dopaminergic synapse (<i>p</i> = 0.003), regulation of lipolysis in adipocytes (<i>p</i> = 0.004), biosynthesis of cofactors (<i>p</i> = 0.004), thyroid hormone synthesis (<i>p</i> = 0.008), aldosterone synthesis and secretion (<i>p</i> = 0.001), taurine and hypotaurine metabolism (<i>p</i> = 0.011), ovarian steroidogenesis (<i>p</i> = 0.011), and the cAMP signaling pathway (<i>p</i> = 0.011) were significantly enriched in differentially expressed metabolites (DEMs). Complement C3 (<i>p</i> = 0.004), platelet factor 4 (<i>p</i> = 0.015), KRT10 (<i>p</i> = 0.004), KRT14 (<i>p</i> = 0.004), beta-estradiol (<i>p</i> = 0.019), testosterone (<i>p</i> = 0.023), sphingosine (<i>p</i> < 0.001), and 1-stearoyl-2-arachidonoyl-sn-glycerol (<i>p</i> = 0.039) could be the monitoring and therapeutic targets for AIMSS. Conclusions: This study offered new insights into the mechanisms underlying musculoskeletal symptoms associated with aromatase inhibitors. It also highlighted potential biomarkers for predicting and addressing these symptoms in breast cancer patients, paving the way for improved intervention strategies.https://www.mdpi.com/2218-1989/15/3/153breast neoplasmsaromatase inhibitorsmusculoskeletal symptomsproteomicsmetabolomicsbiomarkers |
| spellingShingle | Feng Jing Lingyun Jiang Yuling Cao Maoting Tian Jiajia Qiu Jing Zhang Lichen Tang Renquan Lu Yan Hu Plasma Proteomics and Metabolomics of Aromatase Inhibitors-Related Musculoskeletal Syndrome in Early Breast Cancer Patients Metabolites breast neoplasms aromatase inhibitors musculoskeletal symptoms proteomics metabolomics biomarkers |
| title | Plasma Proteomics and Metabolomics of Aromatase Inhibitors-Related Musculoskeletal Syndrome in Early Breast Cancer Patients |
| title_full | Plasma Proteomics and Metabolomics of Aromatase Inhibitors-Related Musculoskeletal Syndrome in Early Breast Cancer Patients |
| title_fullStr | Plasma Proteomics and Metabolomics of Aromatase Inhibitors-Related Musculoskeletal Syndrome in Early Breast Cancer Patients |
| title_full_unstemmed | Plasma Proteomics and Metabolomics of Aromatase Inhibitors-Related Musculoskeletal Syndrome in Early Breast Cancer Patients |
| title_short | Plasma Proteomics and Metabolomics of Aromatase Inhibitors-Related Musculoskeletal Syndrome in Early Breast Cancer Patients |
| title_sort | plasma proteomics and metabolomics of aromatase inhibitors related musculoskeletal syndrome in early breast cancer patients |
| topic | breast neoplasms aromatase inhibitors musculoskeletal symptoms proteomics metabolomics biomarkers |
| url | https://www.mdpi.com/2218-1989/15/3/153 |
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