Cathepsins and their role in gynecological cancers: Evidence from two-sample Mendelian randomization analysis

Medicine, Год журнала: 2025, Номер 104(10), С. e41653 - e41653

Опубликована: Март 7, 2025

Prior studies have reported connections between cathepsins (CTS) and gynecological cancers; however, the exact causal links are yet to be fully understood. Leveraging publicly accessible genome-wide association study summary datasets, we performed a two-sample bidirectional Mendelian randomization (MR) multivariate MR (MVMR) analysis, with inverse variance weighted (IVW) method as primary approach. analysis demonstrated associations CTSB cervical cancer (IVW: odds ratio [OR] = 0.9995, 95% confidence interval [CI] 0.9991-0.9999, P .0418), CTSE ovarian OR 0.9197, CI 0.8505-0.9944, .0358), CTSZ 0.9449, 0.8938-0.9990, .0459), high grade serous 0.8939, 0.8248-0.9689, .0063), 0.9269, 0.8667-0.9913, .0268). A positive correlation was identified CTSH clear cell 1.1496, 1.0368-1.2745, .0081). Nevertheless, subsequent adjustment for false discovery rate revealed that none of P-values retained statistical significance (PFDR > 0.05). MVMR results elucidated inversely associated 0.9988, 0.9981-0.9996, .0022). Moreover, noted CTSF 1.0007, 1.0000-1.0014, .0364), similarly, CTSS 1.0005, 1.0000-1.0011, .0490). CTSO exhibited non-endometrioid endometrial 1.4405, 1.1864-1.7490, < .001), positively 1.1167, 1.0131-1.2310, .0263). The findings reveal emerges protective element against cancer, whereas represent risk factors this disease. stands out factor acts cancer. This elucidates causative CTS cancers, providing innovative insights diagnostic therapeutic optimization.

Язык: Английский

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Exploring therapeutic and diagnostic potential of cysteine cathepsin as targets for cancer therapy with nanomedicine

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 144324 - 144324

Опубликована: Май 1, 2025

Язык: Английский

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Cathepsin H deficiency leads to myopic phenotype in mice

Experimental Eye Research, Год журнала: 2025, Номер unknown, С. 110447 - 110447

Опубликована: Май 1, 2025

Язык: Английский

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Multi-Level Proteomics Reveals Epigenetic Signatures in BCG-mediated Macrophage Activation

Molecular & Cellular Proteomics, Год журнала: 2024, Номер unknown, С. 100851 - 100851

Опубликована: Окт. 1, 2024

Язык: Английский

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Association between cathepsins and skin cancers: A bidirectional two‐sample Mendelian randomization study

Skin Research and Technology, Год журнала: 2024, Номер 30(8)

Опубликована: Авг. 1, 2024

Abstract Background Several cathepsins have been identified as being involved in the development of cancer. Nevertheless, connection between and skin cancers remained highly elusive. Methods A bidirectional Mendelian randomization (MR) analysis was performed to investigate causal association malignancies. The genome‐wide studies (GWAS) data for cathepsins, malignant melanoma (MM), basal cell carcinoma (BCC) were obtained from European research. primary method employed inverse variance weighted. In addition, MR‐Egger, weighted median, mode, simple mode also executed. Sensitivity using Cochran's Q test, MR‐PRESSO. Results From univariable MR (UVMR), cathepsin H, S determined a relationship with BCC. Additionally, H associated MM. Multivariable (MVMR) showed that after correcting risk factors carcinoma, detected be protective against BCC, whereas has observed factor No substantial pleiotropy heterogeneity sensitivity analysis. Conclusion This study first establish direct link Cathepsin potential serve new biomarkers offering valuable assistance prompt identification, treatment, prevention disease. additional clinical trials are required validate our findings.

Язык: Английский

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Identifying and Validating Extracellular Matrix-Related Gene CTSH in Diabetic Foot Ulcer Using Bioinformatics and Machine Learning

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 5871 - 5887

Опубликована: Авг. 1, 2024

Background: Diabetic foot ulcer (DFU) is a serious clinical problem with high amputation and mortality rates, yet there lack of desirable therapy.While the extracellular matrix (ECM) contributes significantly to wound healing, ECM-related biomarker for DFU still unknown.The study was designed identify in using bioinformatics machine learning validate it STZ-induced mice models.Methods: GSE80178 GSE134431 microarray datasets were fetched from GEO database, differentially expressed genes (DEGs) analysis performed, respectively.By analyzing DEGs ECM genes, we identified DEGs, functional enrichment conducted.Subsequently, three algorithms (LASSO, RF SVM-RFE) applied filter key biomarkers.Next, conducted immune infiltration analysis, GSEA, correlation explore hub gene underlying mechanism.A lncRNA-miRNA-mRNA drug regulatory network constructed.Finally, validated models.Results: One hundred forty-five common adult between two identified.Taking intersection 145 964 13 DEGs.Thirteen mainly enriched pathways associated tissue remodeling, inflammation defense against infectious agents.Ultimately, CTSH as biomarker.CTSH difference cells during occurrence development DFU, influenced hedgehog, IL-17 TNF signaling pathway.Additionally, expression correlated many ECM-and immune-related genes.A constructed 10 lncRNAs, 2 miRNAs, 1 drug.Finally, animal models.Conclusion: Our found that can be used both diagnostic prognostic purposes might potential therapeutic target.

Язык: Английский

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Can alterations in cathepsin levels restrain the development of skin cancer?: A bidirectional multivariate Mendelian-randomization study

Medicine, Год журнала: 2024, Номер 103(38), С. e39628 - e39628

Опубликована: Сен. 20, 2024

Malignant skin tumors mainly include basal cell carcinoma, squamous and malignant melanoma. There is currently observational research suggesting that changes in cathepsin (CTS) may be a factor the development of tumors, but no studies have yet demonstrated causal relationship between tissue protease occurrence tumors. Current shown involved tumor invasion metastasis by regulating growth factors cellular immune function microenvironment, decomposing extracellular matrix basement membrane, promoting angiogenesis. In this study, we conducted bidirectional Mendelian-randomization study using publicly available genome-wide association (GWAS; GWAS Catalog) data. This applies multivariate Mendelian randomization (MR) approach to investigate cathepsin, cases where multiple cathepsins are implicated as etiological certain diseases, multivariable analysis assess direct indirect effects exposure factors. present comprehensive MR 9 Based on our largest Catalog dataset available, able draw relatively reliable conclusions. found L2 can promote cancer, Cathepsin O, F associated with an increased risk carcinoma. H inhibit carcinoma reverse it was cause increase O expression. analysis, reducing cancer melanoma, apparent non-melanoma cancer. has dual impact cells, expression different at edge indicate developmental tendencies serve effective biomarkers for predicting

Язык: Английский

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Causal effect of immune cells, metabolites, cathepsins, and vitamin therapy in diabetic retinopathy: a Mendelian randomization and cross-sectional study

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Окт. 1, 2024

Background Diabetic retinopathy (DR) is a major microvascular complication of diabetes and leading cause blindness worldwide. The pathogenesis DR involves complex interactions between metabolic disturbances, immune cells, proteolytic enzymes such as cathepsins (CATs). Despite various studies, the precise roles different CATs, metabolites, vitamins in remain unclear. Method In this study, we employed Mendelian Randomization (MR) to assess causal relationships using genetic instruments selected based on genome-wide association studies (GWAS). We two-sample mediation MR explore effects nine vitamins, DR. Additionally, study also incorporated data from NHANES survey associated relationship utilized cross-sectional analyze vitamin intake diabetic (DR), adjusting for potential confounders strengthen validity our findings. Results analysis identified CAT H significant risk factor both NPDR PDR, with no evidence reverse causality. 62 cell traits were found have 49 PDR. Enrichment revealed that pathways sphingolipid metabolism are crucial progression. Vitamins B6 E significantly reduced Cross-sectional indicated B1, B2, B6, B12, progressively decreased severity. Conclusion This first identify key DR, while showed protective effects, particularly against These findings suggest H, along E, could serve therapeutic targets Further validation through larger, multi-center recommended enhance accuracy applicability these

Язык: Английский

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Acid Sphingomyelinase Deficiency Type B Patient-Derived Liver Organoids Reveals Altered Lysosomal Gene Expression and Lipid Homeostasis

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(16), С. 12645 - 12645

Опубликована: Авг. 10, 2023

Acid sphingomyelinase deficiency (ASMD) or Niemann–Pick disease type A (NPA), B (NPB) and A/B (NPA/B), is a rare lysosomal storage characterized by progressive accumulation of sphingomyelin (SM) in the liver, lungs, bone marrow and, severe cases, neurons. model was established generating liver organoids from NPB patient carrying p.Arg610del variant SMPD1 gene. Liver were transcriptomic lipidomic analysis. We observed altered lipid homeostasis patient-derived showing predictable increase (SM), together with cholesterol esters (CE) triacylglycerides (TAG), reduction phosphatidylcholine (PC) cardiolipins (CL). Analysis gene expression pointed to 24 downregulated genes, including SMPD1, 26 upregulated genes that reflect stress typical disease. Altered revealed reduced enzymes could be involved hepatocytes sphyngoglycolipids glycoproteins, as well coding for different glycosidases cathepsins. Lipidic transcriptome changes support use hepatic ideal models ASMD investigation.

Язык: Английский

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A Mendelian randomization study: Association of Cathepsin with Osteoarticular Muscle Diseases

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Янв. 3, 2024

Abstract Objective: The cathepsin present in lysosomal cells may be closely related to bone, muscle & joint diseases (BMJD)including osteoporosis and osteoarthritis, but its specific mechanism of action still needs further research exploration. aim this study is use a two-sample Mendelian randomization (MR) comprehensive analysis explore the causal relationship between risk BMJD. Method: Based on published genetic data, used method causality morbidity 9 cathepsins with rheumatoid arthritis, ankylosing spondylitis, peripheral arthritis(Crohn's disease, ulcerative colitis, postdysentery disease), psoriatic lower back pain, spinal stenosis, osteoporosis, bone necrosis, connective tissue cartilage diseases, benign tumors, myositis, synovitis tenosynovitis (radial styloid tenosynovitis), shoulder periarthritis, neuromuscular junction atrophy. Meanwhile, order reveal possibility reverse causality, we conducted analysis,using Cochran's Q test MR Egger intercept evaluate heterogeneity, horizontal pleiotropy,and stability SNPs. Result: found that B negatively correlated colitis E positively musculoskeletal G L2 Cathepsin S arthritis; through analysis, lead an increase B. In addition, did not find any synovitis, tenosynovitis, neuritis, osteoporosis,Crohn's arthritis,dysentery low pain,and cathepsin. Conclusion: large-scale population studies GWAS demonstrated close BMJD from perspective, which provide basis for pathogenesis new directions future treatment strategies.

Язык: Английский

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