The causal effect of serum amino acids on the risk of prostate cancer: a two-sample mendelian randomization study
Abstract Prostate cancer (PCa) is the second most common malignancy affecting men globally. Recent advances in metabolomics have highlighted significant alterations in specific amino acid (AA) metabolism linked to PCa, indicating their potential utility in diagnosis and therapy. However, no direct c...
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Nature Portfolio
2024-11-01
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| Online Access: | https://doi.org/10.1038/s41598-024-80986-y |
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| author | Long Miao Qichao Wang Sen Kan Wanqi Liu Yijing Zhang Wei Chen Nienie Qi Xiliang Cao |
| author_facet | Long Miao Qichao Wang Sen Kan Wanqi Liu Yijing Zhang Wei Chen Nienie Qi Xiliang Cao |
| author_sort | Long Miao |
| collection | DOAJ |
| description | Abstract Prostate cancer (PCa) is the second most common malignancy affecting men globally. Recent advances in metabolomics have highlighted significant alterations in specific amino acid (AA) metabolism linked to PCa, indicating their potential utility in diagnosis and therapy. However, no direct causal association between serum AA levels and PCa risk has been established. A total of 35 patients with PCa and 30 individuals with benign prostatic hyperplasia (BPH) were recruited for this study. Targeted metabolomic analysis was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry on serum samples. Two-sample Mendelian randomization (MR) was applied to explore potential causal links between serum AA levels and PCa risk, including mediator effects using dual-phase MR and assessing reverse causality through reverse MR. Results Targeted metabolomic profiling identified six amino acids—glutamate (Glu), Ser, histidine (His), arginine (Arg), aspartic acid (Asp), and glycine (Gly)—that showed significant area under the ROC curve in differentiating between BPH and PCa cases. Notably, Glu demonstrated an inverse association with PCa risk, distinct from the other AAs identified. However, definitive evidence supporting a causal relationship between low Glu levels and increased PCa risk was not observed. Our results suggest a protective role of Glu against PCa development, which may have implications for disease prognosis. Increasing dietary Glu intake may present a potential preventive or therapeutic approach for PCa. |
| format | Article |
| id | doaj-art-a52d6a417d02446c8ed1b63441c7f1ca |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-a52d6a417d02446c8ed1b63441c7f1ca2025-08-20T02:49:17ZengNature PortfolioScientific Reports2045-23222024-11-0114111110.1038/s41598-024-80986-yThe causal effect of serum amino acids on the risk of prostate cancer: a two-sample mendelian randomization studyLong Miao0Qichao Wang1Sen Kan2Wanqi Liu3Yijing Zhang4Wei Chen5Nienie Qi6Xiliang Cao7Department of Urology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical UniversityDepartment of Urology, Xuzhou Cancer HospitalDepartment of Nephrology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical UniversityDepartment of Urology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical UniversityDepartment of Urology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical UniversityDepartment of Urology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical UniversityDepartment of Urology, The Affiliated Hospital of Xuzhou Medical UniversityDepartment of Urology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical UniversityAbstract Prostate cancer (PCa) is the second most common malignancy affecting men globally. Recent advances in metabolomics have highlighted significant alterations in specific amino acid (AA) metabolism linked to PCa, indicating their potential utility in diagnosis and therapy. However, no direct causal association between serum AA levels and PCa risk has been established. A total of 35 patients with PCa and 30 individuals with benign prostatic hyperplasia (BPH) were recruited for this study. Targeted metabolomic analysis was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry on serum samples. Two-sample Mendelian randomization (MR) was applied to explore potential causal links between serum AA levels and PCa risk, including mediator effects using dual-phase MR and assessing reverse causality through reverse MR. Results Targeted metabolomic profiling identified six amino acids—glutamate (Glu), Ser, histidine (His), arginine (Arg), aspartic acid (Asp), and glycine (Gly)—that showed significant area under the ROC curve in differentiating between BPH and PCa cases. Notably, Glu demonstrated an inverse association with PCa risk, distinct from the other AAs identified. However, definitive evidence supporting a causal relationship between low Glu levels and increased PCa risk was not observed. Our results suggest a protective role of Glu against PCa development, which may have implications for disease prognosis. Increasing dietary Glu intake may present a potential preventive or therapeutic approach for PCa.https://doi.org/10.1038/s41598-024-80986-yProstate cancerGlutamateTwo-sampleMendelian randomizationProtective factors |
| spellingShingle | Long Miao Qichao Wang Sen Kan Wanqi Liu Yijing Zhang Wei Chen Nienie Qi Xiliang Cao The causal effect of serum amino acids on the risk of prostate cancer: a two-sample mendelian randomization study Scientific Reports Prostate cancer Glutamate Two-sample Mendelian randomization Protective factors |
| title | The causal effect of serum amino acids on the risk of prostate cancer: a two-sample mendelian randomization study |
| title_full | The causal effect of serum amino acids on the risk of prostate cancer: a two-sample mendelian randomization study |
| title_fullStr | The causal effect of serum amino acids on the risk of prostate cancer: a two-sample mendelian randomization study |
| title_full_unstemmed | The causal effect of serum amino acids on the risk of prostate cancer: a two-sample mendelian randomization study |
| title_short | The causal effect of serum amino acids on the risk of prostate cancer: a two-sample mendelian randomization study |
| title_sort | causal effect of serum amino acids on the risk of prostate cancer a two sample mendelian randomization study |
| topic | Prostate cancer Glutamate Two-sample Mendelian randomization Protective factors |
| url | https://doi.org/10.1038/s41598-024-80986-y |
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