Cisplatin is widely used as a conventional chemotherapy drug for lung adenocarcinoma (LUAD) patients. However, the chemical resistance greatly limits its therapeutic potential. The study aimed to uncover the specific role and new mechanisms of CPT1B in the cisplatin resistance of LUAD. Bioinformatics analysis was utilized to analyze the expression level and enriched pathway of CPT1B in LUAD. The expression of CPT1B in LUAD cells was determined by utilizing quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB). The cisplatin resistance in LUAD was measured with IC50 values obtained from the CCK-8 assay. We used the corresponding reagent kit and WB analysis to determine the levels of triglycerides, cholesterol, phospholipids, fatty acid β-oxidation (FAO) rate, and expression of lipid metabolism-related proteins. Finally, the regulation relationship between CPT1B and ZNF263 was confirmed through bioinformatics analysis, dual-luciferase, and chromatin immunoprecipitation assays. The present investigation revealed that CPT1B was upregulated in LUAD, participating in fatty acid metabolism pathways. In vitro studies have shown that upregulation of CPT1B promoted cisplatin resistance in LUAD cells. This promotion effect induced by the high expression of CPT1B on cisplatin resistance in LUAD was weakened after the addition of the FAO inhibitor Etomoxir. Mechanistically, ZNF263 was capable of binding to the promoter of CPT1B to activate its transcription, thereby enhancing FAO and promoting cisplatin resistance in LUAD cells. In summary, ZNF263 enhances cisplatin resistance in LUAD cells by upregulating CPT1B expression. This study enriches the molecular mechanisms of LUAD chemotherapy resistance and provides new directions for exploring therapeutic targets for LUAD.
{"title":"The ZNF263/CPT1B axis regulates fatty acid β-oxidation to affect cisplatin resistance in lung adenocarcinoma","authors":"Renhe Yan, Caibin Zheng, Suting Qian, Kezhi Li, Xiangsheng Kong, Shunhang Liao","doi":"10.1038/s41397-024-00355-w","DOIUrl":"10.1038/s41397-024-00355-w","url":null,"abstract":"Cisplatin is widely used as a conventional chemotherapy drug for lung adenocarcinoma (LUAD) patients. However, the chemical resistance greatly limits its therapeutic potential. The study aimed to uncover the specific role and new mechanisms of CPT1B in the cisplatin resistance of LUAD. Bioinformatics analysis was utilized to analyze the expression level and enriched pathway of CPT1B in LUAD. The expression of CPT1B in LUAD cells was determined by utilizing quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB). The cisplatin resistance in LUAD was measured with IC50 values obtained from the CCK-8 assay. We used the corresponding reagent kit and WB analysis to determine the levels of triglycerides, cholesterol, phospholipids, fatty acid β-oxidation (FAO) rate, and expression of lipid metabolism-related proteins. Finally, the regulation relationship between CPT1B and ZNF263 was confirmed through bioinformatics analysis, dual-luciferase, and chromatin immunoprecipitation assays. The present investigation revealed that CPT1B was upregulated in LUAD, participating in fatty acid metabolism pathways. In vitro studies have shown that upregulation of CPT1B promoted cisplatin resistance in LUAD cells. This promotion effect induced by the high expression of CPT1B on cisplatin resistance in LUAD was weakened after the addition of the FAO inhibitor Etomoxir. Mechanistically, ZNF263 was capable of binding to the promoter of CPT1B to activate its transcription, thereby enhancing FAO and promoting cisplatin resistance in LUAD cells. In summary, ZNF263 enhances cisplatin resistance in LUAD cells by upregulating CPT1B expression. This study enriches the molecular mechanisms of LUAD chemotherapy resistance and provides new directions for exploring therapeutic targets for LUAD.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 6","pages":"1-8"},"PeriodicalIF":2.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-08DOI: 10.1038/s41397-024-00353-y
Samuel Huxley, James Moriarty, Mark A. Hlatky, Ryan Lennon, Kent Bailey, Malcolm Bell, Nancy Geller, Amir Lerman, Verghese Mathew, Yves Rosenberg, Michael Farkouh, Charanjit Rihal, Bijan Borah, Naveen L. Pereira
CYP2C19 loss of function (LOF) carriers undergoing percutaneous coronary intervention (PCI) have an increased risk of ischemic events when treated with clopidogrel. PCI patients in TAILOR-PCI were randomized to clopidogrel or genotype-guided (GG) therapy in which LOF carriers received ticagrelor and non-carriers clopidogrel. Direct medical costs associated with a GG approach have not been described before. TAILOR-PCI participants for whom direct medical costs were available for the duration from the date of PCI to one-year post PCI were included. Primary cost estimates were obtained from the Mayo Clinic Cost Data Warehouse. There were no differences in direct medical costs between the GG and clopidogrel groups (mean $20,682 versus $19,747, p = 0.11) however total costs were greater in the GG group (mean $21,245 versus $19,891, p = 0.02) which was primarily driven by ticagrelor costs. In conclusion the increased expense of a GG strategy post PCI as compared to clopidogrel for all is primarily driven by the cost of ticagrelor.
{"title":"Cost analysis of CYP2C19 genetic testing in percutaneous coronary intervention patients","authors":"Samuel Huxley, James Moriarty, Mark A. Hlatky, Ryan Lennon, Kent Bailey, Malcolm Bell, Nancy Geller, Amir Lerman, Verghese Mathew, Yves Rosenberg, Michael Farkouh, Charanjit Rihal, Bijan Borah, Naveen L. Pereira","doi":"10.1038/s41397-024-00353-y","DOIUrl":"10.1038/s41397-024-00353-y","url":null,"abstract":"CYP2C19 loss of function (LOF) carriers undergoing percutaneous coronary intervention (PCI) have an increased risk of ischemic events when treated with clopidogrel. PCI patients in TAILOR-PCI were randomized to clopidogrel or genotype-guided (GG) therapy in which LOF carriers received ticagrelor and non-carriers clopidogrel. Direct medical costs associated with a GG approach have not been described before. TAILOR-PCI participants for whom direct medical costs were available for the duration from the date of PCI to one-year post PCI were included. Primary cost estimates were obtained from the Mayo Clinic Cost Data Warehouse. There were no differences in direct medical costs between the GG and clopidogrel groups (mean $20,682 versus $19,747, p = 0.11) however total costs were greater in the GG group (mean $21,245 versus $19,891, p = 0.02) which was primarily driven by ticagrelor costs. In conclusion the increased expense of a GG strategy post PCI as compared to clopidogrel for all is primarily driven by the cost of ticagrelor.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 6","pages":"1-7"},"PeriodicalIF":2.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-07DOI: 10.1038/s41397-024-00352-z
Soroush Mohammadi Jouabadi, Payam Peymani, Mitra Nekouei Shahraki, Jeroen G. J. van Rooij, Linda Broer, Anton J. M. Roks, Bruno H. Stricker, Fariba Ahmadizar
Our study investigated the impact of genetic variations on metformin glycemic response in a cohort from the Rotterdam Study, comprising 14,926 individuals followed for up to 27 years. Among 1285 metformin users of European ancestry, using linear mixed models, we analyzed the association of single nucleotide polymorphisms (SNPs) and a Polygenic Risk Score (PRS) with glycemic response, measured by changes in metformin dosage or HbA1c levels. While individual genetic variants showed no significant association, rs622342 on SLC2A1 correlated with increased glycemic response only in metformin monotherapy patients (β = −2.09, P-value < 0.001). The collective effect of variants, as represented by PRS, weakly correlated with changes in metformin dosage (β = 0.023, P-value = 0.027). Synergistic interaction was observed between rs7124355 and rs8192675. Our findings suggest that while higher PRS correlates with increased metformin dosage, its modest effect size limits clinical utility, emphasizing the need for future research in diverse populations to refine genetic risk models.
{"title":"Effects and interaction of single nucleotide polymorphisms at the pharmacokinetic/pharmacodynamic site: insights from the Rotterdam study into metformin clinical response and dose titration","authors":"Soroush Mohammadi Jouabadi, Payam Peymani, Mitra Nekouei Shahraki, Jeroen G. J. van Rooij, Linda Broer, Anton J. M. Roks, Bruno H. Stricker, Fariba Ahmadizar","doi":"10.1038/s41397-024-00352-z","DOIUrl":"10.1038/s41397-024-00352-z","url":null,"abstract":"Our study investigated the impact of genetic variations on metformin glycemic response in a cohort from the Rotterdam Study, comprising 14,926 individuals followed for up to 27 years. Among 1285 metformin users of European ancestry, using linear mixed models, we analyzed the association of single nucleotide polymorphisms (SNPs) and a Polygenic Risk Score (PRS) with glycemic response, measured by changes in metformin dosage or HbA1c levels. While individual genetic variants showed no significant association, rs622342 on SLC2A1 correlated with increased glycemic response only in metformin monotherapy patients (β = −2.09, P-value < 0.001). The collective effect of variants, as represented by PRS, weakly correlated with changes in metformin dosage (β = 0.023, P-value = 0.027). Synergistic interaction was observed between rs7124355 and rs8192675. Our findings suggest that while higher PRS correlates with increased metformin dosage, its modest effect size limits clinical utility, emphasizing the need for future research in diverse populations to refine genetic risk models.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 6","pages":"1-8"},"PeriodicalIF":2.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41397-024-00352-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-02DOI: 10.1038/s41397-024-00350-1
Maren S. Fragala, Murray Keogh, Steven E. Goldberg, Raymond A. Lorenz, Jeffrey A. Shaman
Clinical and economic outcomes from a pharmacogenomics-enriched comprehensive medication management program were evaluated over 26 months in a self-insured U.S. employee population (n = 452 participants; n = 1500 controls) using propensity matched pre-post design with adjusted negative binomial and linear regression models. After adjusting for baseline covariates, program participation was associated with 39% fewer inpatient (p = 0.05) and 39% fewer emergency department (p = 0.002) visits, and with 21% more outpatient visits (p < 0.001) in the follow-up period compared to the control group. Results show pharmacogenomics-enriched comprehensive medication management can favorably impact healthcare utilization in a self-insured employer population by reducing emergency department and inpatient visits and can offer the potential for cost savings. Self-insured employers may consider implementing pharmacogenomics-enriched comprehensive medication management to improve the healthcare of their employees.
{"title":"Clinical and economic outcomes of a pharmacogenomics-enriched comprehensive medication management program in a self-insured employee population","authors":"Maren S. Fragala, Murray Keogh, Steven E. Goldberg, Raymond A. Lorenz, Jeffrey A. Shaman","doi":"10.1038/s41397-024-00350-1","DOIUrl":"10.1038/s41397-024-00350-1","url":null,"abstract":"Clinical and economic outcomes from a pharmacogenomics-enriched comprehensive medication management program were evaluated over 26 months in a self-insured U.S. employee population (n = 452 participants; n = 1500 controls) using propensity matched pre-post design with adjusted negative binomial and linear regression models. After adjusting for baseline covariates, program participation was associated with 39% fewer inpatient (p = 0.05) and 39% fewer emergency department (p = 0.002) visits, and with 21% more outpatient visits (p < 0.001) in the follow-up period compared to the control group. Results show pharmacogenomics-enriched comprehensive medication management can favorably impact healthcare utilization in a self-insured employer population by reducing emergency department and inpatient visits and can offer the potential for cost savings. Self-insured employers may consider implementing pharmacogenomics-enriched comprehensive medication management to improve the healthcare of their employees.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 5","pages":"1-6"},"PeriodicalIF":2.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.1038/s41397-024-00349-8
Moataz E. Mohamed, Bin Guo, Baolin Wu, David P. Schladt, Amutha Muthusamy, Weihua Guan, Juan E. Abrahante, Guillaume Onyeaghala, Abdelrahman Saqr, Nathan Pankratz, Gaurav Agarwal, Roslyn B. Mannon, Arthur J. Matas, William S. Oetting, Rory P. Remmel, Ajay K. Israni, Pamala A. Jacobson, DeKAF Genomics and GEN03 Investigators, Casey R. Dorr
African American (AA) kidney transplant recipients (KTRs) have poor outcomes, which may in-part be due to tacrolimus (TAC) sub-optimal immunosuppression. We previously determined the common genetic regulators of TAC pharmacokinetics in AAs which were CYP3A5 *3, *6, and *7. To identify low-frequency variants that impact TAC pharmacokinetics, we used extreme phenotype sampling and compared individuals with extreme high (n = 58) and low (n = 60) TAC troughs (N = 515 AA KTRs). Targeted next generation sequencing was conducted in these two groups. Median TAC troughs in the high group were 7.7 ng/ml compared with 6.3 ng/ml in the low group, despite lower daily doses of 5 versus 12 mg, respectively. Of 34,542 identified variants across 99 genes, 1406 variants were suggestively associated with TAC troughs in univariate models (p-value < 0.05), however none were significant after multiple testing correction. We suggest future studies investigate additional sources of TAC pharmacokinetic variability such as drug-drug-gene interactions and pharmacomicrobiome.
{"title":"Extreme phenotype sampling and next generation sequencing to identify genetic variants associated with tacrolimus in African American kidney transplant recipients","authors":"Moataz E. Mohamed, Bin Guo, Baolin Wu, David P. Schladt, Amutha Muthusamy, Weihua Guan, Juan E. Abrahante, Guillaume Onyeaghala, Abdelrahman Saqr, Nathan Pankratz, Gaurav Agarwal, Roslyn B. Mannon, Arthur J. Matas, William S. Oetting, Rory P. Remmel, Ajay K. Israni, Pamala A. Jacobson, DeKAF Genomics and GEN03 Investigators, Casey R. Dorr","doi":"10.1038/s41397-024-00349-8","DOIUrl":"10.1038/s41397-024-00349-8","url":null,"abstract":"African American (AA) kidney transplant recipients (KTRs) have poor outcomes, which may in-part be due to tacrolimus (TAC) sub-optimal immunosuppression. We previously determined the common genetic regulators of TAC pharmacokinetics in AAs which were CYP3A5 *3, *6, and *7. To identify low-frequency variants that impact TAC pharmacokinetics, we used extreme phenotype sampling and compared individuals with extreme high (n = 58) and low (n = 60) TAC troughs (N = 515 AA KTRs). Targeted next generation sequencing was conducted in these two groups. Median TAC troughs in the high group were 7.7 ng/ml compared with 6.3 ng/ml in the low group, despite lower daily doses of 5 versus 12 mg, respectively. Of 34,542 identified variants across 99 genes, 1406 variants were suggestively associated with TAC troughs in univariate models (p-value < 0.05), however none were significant after multiple testing correction. We suggest future studies investigate additional sources of TAC pharmacokinetic variability such as drug-drug-gene interactions and pharmacomicrobiome.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 5","pages":"1-9"},"PeriodicalIF":2.9,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.1038/s41397-024-00348-9
Christine M. Formea, Paldeep Atwal, Kathryn Meintsma, Martin Dawes, Gary Marchant, Ben L. Kong, J. Shawn Jones, Sara L. Rogers
{"title":"STRIPE partners in precision medicine series: provider perspective","authors":"Christine M. Formea, Paldeep Atwal, Kathryn Meintsma, Martin Dawes, Gary Marchant, Ben L. Kong, J. Shawn Jones, Sara L. Rogers","doi":"10.1038/s41397-024-00348-9","DOIUrl":"10.1038/s41397-024-00348-9","url":null,"abstract":"","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 5","pages":"1-4"},"PeriodicalIF":2.9,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-15DOI: 10.1038/s41397-024-00345-y
Sara L. Rogers, J. Shawn Jones, Ben L. Kong, Christine M. Formea, Jacob Awkal, Benjamin G. Brown
{"title":"A collaborative force for precision medicine progress: the STRIPE pharmacogenomics conference series","authors":"Sara L. Rogers, J. Shawn Jones, Ben L. Kong, Christine M. Formea, Jacob Awkal, Benjamin G. Brown","doi":"10.1038/s41397-024-00345-y","DOIUrl":"10.1038/s41397-024-00345-y","url":null,"abstract":"","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 5","pages":"1-2"},"PeriodicalIF":2.9,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41397-024-00345-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-14DOI: 10.1038/s41397-024-00347-w
Ben L. Kong, Roseann S. Donnelly, Amina Abubakar, Henry M. Dunnenberger, J. Shawn Jones, Sara L. Rogers, David Kisor
{"title":"STRIPE partners in precision medicine series: pharmacist perspective","authors":"Ben L. Kong, Roseann S. Donnelly, Amina Abubakar, Henry M. Dunnenberger, J. Shawn Jones, Sara L. Rogers, David Kisor","doi":"10.1038/s41397-024-00347-w","DOIUrl":"10.1038/s41397-024-00347-w","url":null,"abstract":"","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 5","pages":"1-3"},"PeriodicalIF":2.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-09DOI: 10.1038/s41397-024-00344-z
John H. McDermott, Videha Sharma, Glenda M. Beaman, Jessica Keen, William G. Newman, Paul Wilson, Katherine Payne, Stuart Wright
Pharmacogenetic testing in the United Kingdom’s National Health Service (NHS) has historically been reactive in nature, undertaken in the context of single gene-drug relationships in specialist settings. Using a discrete choice experiment we aimed to identify healthcare professional preferences for development of a pharmacogenetic testing service in primary care in the NHS. Respondents, representing two professions groups (general practitioners or pharmacists), completed one of two survey versions, asking them to select their preferred pharmacogenetic testing service in the context of a presentation of low mood or joint pain. Responses from 235 individuals were included. All respondents preferred pharmacogenetic testing over no testing, though preference heterogeneity was identified. Both professional groups, but especially GPs, were highly sensitive to service design, with uptake varying depending on the service offered. This study demonstrates uptake of a pharmacogenetic testing service is impacted by service design and highlights key areas which should be prioritised within future initiatives.
{"title":"Understanding general practitioner and pharmacist preferences for pharmacogenetic testing in primary care: a discrete choice experiment","authors":"John H. McDermott, Videha Sharma, Glenda M. Beaman, Jessica Keen, William G. Newman, Paul Wilson, Katherine Payne, Stuart Wright","doi":"10.1038/s41397-024-00344-z","DOIUrl":"10.1038/s41397-024-00344-z","url":null,"abstract":"Pharmacogenetic testing in the United Kingdom’s National Health Service (NHS) has historically been reactive in nature, undertaken in the context of single gene-drug relationships in specialist settings. Using a discrete choice experiment we aimed to identify healthcare professional preferences for development of a pharmacogenetic testing service in primary care in the NHS. Respondents, representing two professions groups (general practitioners or pharmacists), completed one of two survey versions, asking them to select their preferred pharmacogenetic testing service in the context of a presentation of low mood or joint pain. Responses from 235 individuals were included. All respondents preferred pharmacogenetic testing over no testing, though preference heterogeneity was identified. Both professional groups, but especially GPs, were highly sensitive to service design, with uptake varying depending on the service offered. This study demonstrates uptake of a pharmacogenetic testing service is impacted by service design and highlights key areas which should be prioritised within future initiatives.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 5","pages":"1-7"},"PeriodicalIF":2.9,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07DOI: 10.1038/s41397-024-00346-x
Houyi Wei, Zhilong Li, Kaiyu Qian, Wenzhi Du, Lingao Ju, Danni Shan, Mengxue Yu, Yayun Fang, Yi Zhang, Yu Xiao, Gang Wang, Xinghuan Wang
This study utilized Mendelian randomization (MR) analysis and genome-wide association study (GWAS) data to investigate the association between commonly prescribed drugs and bladder cancer (BLCA) risk. Our results revealed that HMG CoA reductase (HMGCR) inhibitors, specifically simvastatin, are significantly associated with reduced BLCA risk. We further showed that simvastatin could significantly inhibit BLCA proliferation and epithelial-mesenchymal transition in animal models, with transcriptomic data identifying several pathways associated with these processes. Higher expression of HMGCR were linked with BLCA development and progression, and certain blood lipids, such as lipoprotein particles and very low density lipoprotein (VLDL) cholesterol, might influence BLCA risk. These findings suggested that HMGCR inhibitors, particularly simvastatin, could be potential treatment options or adjuvant therapies for BLCA.
本研究利用孟德尔随机化（MR）分析和全基因组关联研究（GWAS）数据调查了常用处方药与膀胱癌（BLCA）风险之间的关联。我们的研究结果表明，HMG CoA 还原酶（HMGCR）抑制剂，特别是辛伐他汀，与膀胱癌风险的降低显著相关。我们进一步发现，辛伐他汀能在动物模型中显著抑制BLCA的增殖和上皮-间质转化，转录组数据确定了与这些过程相关的几条通路。HMGCR的高表达与BLCA的发生和发展有关，而某些血脂，如脂蛋白颗粒和极低密度脂蛋白（VLDL）胆固醇，可能会影响BLCA的风险。这些研究结果表明，HMGCR抑制剂，尤其是辛伐他汀，可能是治疗或辅助治疗BLCA的潜在选择。
{"title":"Unveiling the association between HMG-CoA reductase inhibitors and bladder cancer: a comprehensive analysis using Mendelian randomization, animal models, and transcriptomics","authors":"Houyi Wei, Zhilong Li, Kaiyu Qian, Wenzhi Du, Lingao Ju, Danni Shan, Mengxue Yu, Yayun Fang, Yi Zhang, Yu Xiao, Gang Wang, Xinghuan Wang","doi":"10.1038/s41397-024-00346-x","DOIUrl":"10.1038/s41397-024-00346-x","url":null,"abstract":"This study utilized Mendelian randomization (MR) analysis and genome-wide association study (GWAS) data to investigate the association between commonly prescribed drugs and bladder cancer (BLCA) risk. Our results revealed that HMG CoA reductase (HMGCR) inhibitors, specifically simvastatin, are significantly associated with reduced BLCA risk. We further showed that simvastatin could significantly inhibit BLCA proliferation and epithelial-mesenchymal transition in animal models, with transcriptomic data identifying several pathways associated with these processes. Higher expression of HMGCR were linked with BLCA development and progression, and certain blood lipids, such as lipoprotein particles and very low density lipoprotein (VLDL) cholesterol, might influence BLCA risk. These findings suggested that HMGCR inhibitors, particularly simvastatin, could be potential treatment options or adjuvant therapies for BLCA.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 5","pages":"1-12"},"PeriodicalIF":2.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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