Causal links of human serum metabolites on the risk of prostate cancer: insights from genome-wide Mendelian randomization, single-cell RNA sequencing, and metabolic pathway analysis
BackgroundRecently, serum metabolites have shown potential in predicting survival outcomes and may be related to the pathogenesis of prostate cancer. Nevertheless, the precise impact concerning the genetic effect of metabolites on prostate cancer risk remains obscure. In this context, we conducted a...
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Endocrinology |
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| author | Renbing Pan Renbing Pan Jingwen Liu Mingjia Xiao Chuanyang Sun Jianyong Zhu Lijun Wan Boxin Xue |
| author_facet | Renbing Pan Renbing Pan Jingwen Liu Mingjia Xiao Chuanyang Sun Jianyong Zhu Lijun Wan Boxin Xue |
| author_sort | Renbing Pan |
| collection | DOAJ |
| description | BackgroundRecently, serum metabolites have shown potential in predicting survival outcomes and may be related to the pathogenesis of prostate cancer. Nevertheless, the precise impact concerning the genetic effect of metabolites on prostate cancer risk remains obscure. In this context, we conducted a Mendelian randomization (MR) study aiming to explore the causality between genetically determined metabolites and the risk of prostate cancer.MethodsWe conducted a two-sample MR analysis aiming to identify the underlying metabolites associated with prostate cancer. Exposure information was obtained from the largest metabolome-based genome-wide association (GWAS) data containing 7,824 Europeans. Genome-wide association analysis was utilized to detect instrumental variables (IVs) for metabolites. We applied the inverse-variance weighted (IVW) approach as the primary method, and to augment the reliability and robustness of our findings, additional analysis methods encompassing weighted median, MR-Egger, and leave-one-out analysis were utilized. MR-Egger intercept test was implemented to explore the pleiotropy. Cochran’s Q test was utilized to quantify the degree of heterogeneity. Additionally, we performed metabolic pathway analysis and single-cell RNA sequencing analysis.ResultsWe found that three serum metabolites were causally associated with prostate cancer after utilizing rigorous screening standards. Utilizing single nucleotide polymorphisms as IVs, a 1-SD increase in fructose was associated with 77% higher risk of prostate cancer (OR:1.77, 95%CI: 1.05-2.97, PIVW=0.031), a 1-SD increase in N1-methyl-3-pyridone-4-carboxamide was associated with 29% higher risk of prostate cancer (OR:1.29, 95%CI: 1.05-1.58, PIVW=0.017), and a 1-SD increase in 12-hydroxyeicosatetraenoate (12-HETE) was associated with 18% higher risk of prostate cancer (OR:1.18, 95%CI: 1.07-1.31, PIVW=0.0008). Metabolites that were causally linked to the risk of prostate cancer were mainly enriched in the valine, leucine and isoleucine biosynthesis pathway (P=0.026) and the nicotinate and nicotinamide metabolism pathway (P=0.048).ConclusionsOur MR analysis provided suggestive evidence supporting the causal relationships between three identified serum metabolites and prostate cancer, necessitating further investigation to elucidate the underlying mechanisms through which these blood metabolites and metabolic pathways may impact the initiation and progression of prostate cancer. |
| format | Article |
| id | doaj-art-2022de07ee124f008731a5da060112c8 |
| institution | Kabale University |
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| publishDate | 2024-11-01 |
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| spelling | doaj-art-2022de07ee124f008731a5da060112c82024-11-12T13:10:43ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-11-011510.3389/fendo.2024.14433301443330Causal links of human serum metabolites on the risk of prostate cancer: insights from genome-wide Mendelian randomization, single-cell RNA sequencing, and metabolic pathway analysisRenbing Pan0Renbing Pan1Jingwen Liu2Mingjia Xiao3Chuanyang Sun4Jianyong Zhu5Lijun Wan6Boxin Xue7Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartment of Urology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaThe Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaDepartment of Central Laboratory, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaDepartment of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartment of Urology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaDepartment of Urology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaDepartment of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaBackgroundRecently, serum metabolites have shown potential in predicting survival outcomes and may be related to the pathogenesis of prostate cancer. Nevertheless, the precise impact concerning the genetic effect of metabolites on prostate cancer risk remains obscure. In this context, we conducted a Mendelian randomization (MR) study aiming to explore the causality between genetically determined metabolites and the risk of prostate cancer.MethodsWe conducted a two-sample MR analysis aiming to identify the underlying metabolites associated with prostate cancer. Exposure information was obtained from the largest metabolome-based genome-wide association (GWAS) data containing 7,824 Europeans. Genome-wide association analysis was utilized to detect instrumental variables (IVs) for metabolites. We applied the inverse-variance weighted (IVW) approach as the primary method, and to augment the reliability and robustness of our findings, additional analysis methods encompassing weighted median, MR-Egger, and leave-one-out analysis were utilized. MR-Egger intercept test was implemented to explore the pleiotropy. Cochran’s Q test was utilized to quantify the degree of heterogeneity. Additionally, we performed metabolic pathway analysis and single-cell RNA sequencing analysis.ResultsWe found that three serum metabolites were causally associated with prostate cancer after utilizing rigorous screening standards. Utilizing single nucleotide polymorphisms as IVs, a 1-SD increase in fructose was associated with 77% higher risk of prostate cancer (OR:1.77, 95%CI: 1.05-2.97, PIVW=0.031), a 1-SD increase in N1-methyl-3-pyridone-4-carboxamide was associated with 29% higher risk of prostate cancer (OR:1.29, 95%CI: 1.05-1.58, PIVW=0.017), and a 1-SD increase in 12-hydroxyeicosatetraenoate (12-HETE) was associated with 18% higher risk of prostate cancer (OR:1.18, 95%CI: 1.07-1.31, PIVW=0.0008). Metabolites that were causally linked to the risk of prostate cancer were mainly enriched in the valine, leucine and isoleucine biosynthesis pathway (P=0.026) and the nicotinate and nicotinamide metabolism pathway (P=0.048).ConclusionsOur MR analysis provided suggestive evidence supporting the causal relationships between three identified serum metabolites and prostate cancer, necessitating further investigation to elucidate the underlying mechanisms through which these blood metabolites and metabolic pathways may impact the initiation and progression of prostate cancer.https://www.frontiersin.org/articles/10.3389/fendo.2024.1443330/fullserum metabolitesprostate cancerMendelian randomizationsingle-cell RNA-seqmetabolic pathways |
| spellingShingle | Renbing Pan Renbing Pan Jingwen Liu Mingjia Xiao Chuanyang Sun Jianyong Zhu Lijun Wan Boxin Xue Causal links of human serum metabolites on the risk of prostate cancer: insights from genome-wide Mendelian randomization, single-cell RNA sequencing, and metabolic pathway analysis Frontiers in Endocrinology serum metabolites prostate cancer Mendelian randomization single-cell RNA-seq metabolic pathways |
| title | Causal links of human serum metabolites on the risk of prostate cancer: insights from genome-wide Mendelian randomization, single-cell RNA sequencing, and metabolic pathway analysis |
| title_full | Causal links of human serum metabolites on the risk of prostate cancer: insights from genome-wide Mendelian randomization, single-cell RNA sequencing, and metabolic pathway analysis |
| title_fullStr | Causal links of human serum metabolites on the risk of prostate cancer: insights from genome-wide Mendelian randomization, single-cell RNA sequencing, and metabolic pathway analysis |
| title_full_unstemmed | Causal links of human serum metabolites on the risk of prostate cancer: insights from genome-wide Mendelian randomization, single-cell RNA sequencing, and metabolic pathway analysis |
| title_short | Causal links of human serum metabolites on the risk of prostate cancer: insights from genome-wide Mendelian randomization, single-cell RNA sequencing, and metabolic pathway analysis |
| title_sort | causal links of human serum metabolites on the risk of prostate cancer insights from genome wide mendelian randomization single cell rna sequencing and metabolic pathway analysis |
| topic | serum metabolites prostate cancer Mendelian randomization single-cell RNA-seq metabolic pathways |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2024.1443330/full |
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