Identification of therapeutic targets for chronic kidney disease through Mendelian randomization analysis of druggable genes DOI Creative Commons
Raymond Liang, Jian Su,

Xiangqi Wu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 23, 2024

Abstract BACKGROUND Chronic Kidney Disease (CKD) is a multifaceted and gradually advancing condition characterized by complex pathogenesis. The current therapeutic options for CKD remain limited in efficacy. Consequently, the identification exploration of novel drug targets are paramount importance. METHODS We identified cis-expression quantitative trait loci (cis-eQTLs) with potential as from eQTLGen Consortium database to serve exposure. For outcome, we utilized genome-wide association study (GWAS) chronic kidney disease FinnGen database, which comprised case group 11,265 individuals control 436,208 individuals. MR analysis was employed investigate druggable genes closely associated CKD. Subsequently, Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analyses were conducted elucidate functional roles these significant genes. Finally, colocalization determine likelihood that cis-eQTL gene share causal variant. RESULTS expression 12 found be significantly risk, false discovery rate (FDR) less than 0.05. GO KEGG indicated primarily involved regulation MAP kinase activity, protein serine/threonine Gap junction, Platelet activation Oxytocin signaling pathway. results suggested TUBB may variant, posterior probability (PP.H4) exceeding 80% (TUBB: 97.27%). CONCLUSION Compelling statistical evidence indicates represents most promising pharmacological target treatment This not only identifies but also offers valuable insights future development context

Language: Английский

Serum TUBB is a potential biomarker for the diagnosis of non-small cell lung cancer DOI Open Access
Ning Du, Dingli Song, Dapeng Liu

et al.

Journal of Cancer Metastasis and Treatment, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Aim: To identify serum biomarkers for non-small cell lung cancer (NSCLC) and assess their potential early diagnosis. Experimental: MB-WCX coupled with MALDI-TOF MS was utilized to profile samples from 64 NSCLC patients healthy subjects, followed by ClinProTools software Liquid chromatography-electrospray ionization-tandem mass spectrometry(LC-ESI-MS/MS) recognition characterization of differentially expressed peaks. Enzyme-linked immunosorbent assay (ELISA) confirmed protein concentrations, while The Cancer Genome Atlas (TCGA) database leveraged validation candidate in a larger cohort. Results: 39 distinct proteomic m/z peaks were identified five these significantly distinguishing controls (HC). A model developed using the GA (Genetic Algorithm) ClinProt data demonstrated sensitivity 84.72% specificity 88.68% identifying patients. Peaks 2 through 5 observed be downregulated group. Notably, peptide peak, Peak 1, an value 1,866, as fragment TUBB, upregulated NSCLC. ELISA validated increased TUBB levels (P < 0.001). Furthermore, analysis expression tissues TCGA revealed elevated tissues. Conclusions: Serum is diagnostic biomarker NSCLC, which may benefit diagnosis enhance survival rate

Language: Английский

Citations

0
Comprehensive Analysis of GPSM2: From Pan‐Cancer Analysis to Experimental Validation DOI Creative Commons
Chunjiao Yang, Yuzhe Zhang, Lirong Yan

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(7)

Published: April 1, 2025

ABSTRACT G‐protein signalling modulator 2 (GPSM2) plays an important role in maintaining cell polarisation and regulating the cycle; however, a systematic comprehensive analysis of GPSM2 cancer is still lacking. Using extensive multi‐omics data, we explored pan‐cancer expression levels from multiple perspectives its association with prognosis, diagnosis, tumour stemness, immune‐related genes, immune infiltration, genomic instability, response to immunotherapy. We also elucidated potential biological functions using gene set enrichment (GSEA) searched for targeted drugs that affect connectivity map analysis. To elucidate effect on colon cancer, evaluated behaviour two lines. In this study, was systematically analysed shown have satisfactory performance disease diagnosis prognostic prediction various cancers. genesis development tumours diagnostic biomarker as well anti‐cancer therapeutic target.

Language: Английский

Citations

0
Identification of Potential Drug Targets for Immunoglobulin A Nephropathy: A Mendelian Randomization Study DOI Creative Commons

Limei Xiong,

Hui Zhang, Yannan Guo

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 581 - 581

Published: Feb. 25, 2025

Background: The current pharmacological treatments for Immunoglobulin A nephropathy (IgAN) demonstrate limited effectiveness and may cause serious side effects. This study aimed to explore novel potential drug targets IgAN. Methods: We utilized summarized data from a recent genome-wide association on IgAN, cis-expression quantitative trait loci druggable genes obtained the eQTLGen Consortium, DNA methylation derived GoDMC database. Two-sample Mendelian randomization (MR) analysis, Bayesian colocalization, mediation analysis through two-step MR approach were performed investigate their causal relationships. Results: colocalization analyses demonstrated that expression of HLA-DPA1 C4A was associated with an increased risk In contrast, TUBB, CYP21A2, C4B decreased Mediation revealed acted as mediator in relationship between three sites (cg01140143, cg08898074, cg12168509) mediated proportions 33.74% (95% CI 1.64–73.27), 41.67% 20.78–66.97), 50.34% 27.89–74.76), respectively. Conclusions: Several identified show associations IgAN be targeted development. Nevertheless, additional experimental validation is warranted clarify specific roles pathogenesis

Language: Английский

Citations

0
Identification of therapeutic targets for chronic kidney disease through Mendelian randomization analysis of druggable genes DOI Creative Commons
Raymond Liang, Jian Su,

Xiangqi Wu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 28, 2025

Chronic Kidney Disease (CKD) is a multifaceted and gradually advancing condition characterized by complex pathogenesis. The current therapeutic options for CKD remain limited in efficacy. Consequently, the identification exploration of novel drug targets are paramount importance. We identified cis-expression quantitative trait loci (cis-eQTLs) with potential as from eQTLGen Consortium database to serve exposure. For outcome, we utilized genome-wide association study (GWAS) chronic kidney disease FinnGen database, which comprised case group 11,265 individuals control 436,208 individuals. MR analysis was employed investigate druggable genes closely associated CKD. Subsequently, Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analyses were conducted elucidate functional roles these significant genes. Finally, colocalization determine likelihood that cis-eQTL gene share causal variant. expression 12 found be significantly risk, false discovery rate (FDR) less than 0.05. GO KEGG indicated primarily involved regulation MAP kinase activity, protein serine/threonine Gap junction, Platelet activation Oxytocin signaling pathway. results suggested TUBB may variant, posterior probability (PP.H4) exceeding 80% (TUBB: 97.27%). Compelling statistical evidence indicates represents most promising pharmacological target treatment This not only identifies but also offers valuable insights future development context

Language: Английский

Citations

0
Comprehensive Pan-cancer Analysis Revealed CASP10 As a Promising Biomarker For Diverse Tumor Types DOI Creative Commons
Qian Wang,

Yaping Jiang,

Weijia Liao

et al.

International Journal of Immunopathology and Pharmacology, Journal Year: 2025, Volume and Issue: 39

Published: March 1, 2025

We aimed to explore the comprehensive cancer landscape of Caspase-10 (CASP10). CASP10, a member caspase family, is located at human chromosome locus 2q33-34. Studies have suggested its potential role in development certain cancers. To evaluate CASP10 expression normal and pan-cancer tissues, we integrated data from The Cancer Genome Atlas (TCGA), GEO, Human Protein (HPA), UALCAN databases. diagnostic prognostic significance was analyzed using Receiver Operating Characteristic (ROC), Cox regression, Kaplan-Meier analysis. Correlations with clinical parameters were assessed via Wilcoxon test, Kruskal-Wallis logistic regression Genomic variations explored cBioPortal, GSCALite database, LinkedOmics database used detect function pan-cancer. Interactions between Tumor Immune Microenvironment (TIME) investigated TISIDB, TIMER2, TISCH utilized assess sensitivity small-molecule drugs. In addition, Western Blotting (WB) employed our Liver Hepatocellular Carcinoma (LIHC) Stomach Adenocarcinoma (STAD) cohorts. transcription protein significantly differ across types, marking it as biomarker for diagnosis prognosis. Its correlated characteristics such histological types Alpha-Fetoprotein (AFP) levels. gene exhibited 2% alteration frequency patients, significant SNV CNV profiles, decreased methylation closely related Nuclear Factor-κappa B (NF-κB), TNF, cell cycle, JAK-STAT signal pathways. showed correlation immune components tumor microenvironment, including lymphocytes, stimulators, inhibitors, MHC molecules, chemokines, receptors, Cancer-Associated Fibroblasts (CAFs). Importantly, could predict diverse anti-cancer Finally, WB analysis validated overexpression LIHC STAD tissues. Our bioinformatic reveal on diagnosis, prognosis, progression types.

Language: Английский

Citations

0
Identification of therapeutic targets for chronic kidney disease through Mendelian randomization analysis of druggable genes DOI Creative Commons
Raymond Liang, Jian Su,

Xiangqi Wu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 23, 2024

Abstract BACKGROUND Chronic Kidney Disease (CKD) is a multifaceted and gradually advancing condition characterized by complex pathogenesis. The current therapeutic options for CKD remain limited in efficacy. Consequently, the identification exploration of novel drug targets are paramount importance. METHODS We identified cis-expression quantitative trait loci (cis-eQTLs) with potential as from eQTLGen Consortium database to serve exposure. For outcome, we utilized genome-wide association study (GWAS) chronic kidney disease FinnGen database, which comprised case group 11,265 individuals control 436,208 individuals. MR analysis was employed investigate druggable genes closely associated CKD. Subsequently, Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analyses were conducted elucidate functional roles these significant genes. Finally, colocalization determine likelihood that cis-eQTL gene share causal variant. RESULTS expression 12 found be significantly risk, false discovery rate (FDR) less than 0.05. GO KEGG indicated primarily involved regulation MAP kinase activity, protein serine/threonine Gap junction, Platelet activation Oxytocin signaling pathway. results suggested TUBB may variant, posterior probability (PP.H4) exceeding 80% (TUBB: 97.27%). CONCLUSION Compelling statistical evidence indicates represents most promising pharmacological target treatment This not only identifies but also offers valuable insights future development context

Language: Английский

Citations

0