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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Main Authors: Long Miao, Qichao Wang, Sen Kan, Wanqi Liu, Yijing Zhang, Wei Chen, Nienie Qi, Xiliang Cao
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Scientific Reports
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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.
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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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