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Title:
Identification of novel susceptibility loci for testicular germ cell tumors through multi-omics analysis | Discover Oncology
Description:
Objective This study aimed to identify potential susceptibility loci for testicular germ cell tumors (TGCT) through a comprehensive multi-omics analysis. Methods A Mendelian randomization (MR) analysis was conducted to investigate the causal relationships between immune cell phenotypes and TGCT. Summary-based Mendelian Randomization (SMR) and colocalization analyses were subsequently performed to examine candidate phenotypes and TGCT using quantitative trait locis from multiple datasets. Differential gene expression analysis was employed to explore the immune landscape of the target gene in the TGCT tumor microenvironment using UCSC databases. Additionally, potential pathway mechanisms were investigated to elucidate the functional role of candidate genes. Results MR analysis identified a significant causal association between the immune cell phenotype HLA-DR on monocytes and TGCT (p = 0.02). SMR analysis revealed that BDH2 was significantly associated with TGCT susceptibility (OR = 0.597, p = 2.21e-07). Colocalization analysis suggested shared genetic variation between BDH2 and TGCT (PP.H4 = 0.95). Immunohistochemistry staining confirmed that BDH2 mRNA levels were significantly lower in TGCT tissues than in normal controls (p < 0.001). In the TGCT tumor microenvironment, lower BDH2 expression was associated with higher immune scores, with T cells and B cells predominantly enriched in the low-expression group, whereas monocytes and endothelial cells were more abundant in the high-expression group. Furthermore, members of the HLA family, exhibited significant correlations between their methylation levels and low BDH2 expression groups. Pathway analysis indicated that BDH2 may influence TGCT progression through the RAS-MAPK signaling pathway. Conclusions Our findings support a significant susceptibility relationship between the phenotype HLA-DR on monocytes, BDH2, and TGCT.
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Keywords {🔍}
expression, bdh, pubmed, tgct, article, google, scholar, analysis, immune, cell, cancer, gene, cas, central, levels, testicular, fig, tumor, cells, data, cohort, hladr, methylation, significant, analyses, pathway, genetic, germ, genes, protein, correlation, potential, mendelian, randomization, identified, association, rasmapk, tumors, causal, colocalization, relationship, study, pph, dna, susceptibility, smr, including, tissues, findings, loci,
Topics {✒️}
ten cancer-related pathways—tsc/mtor gov/ccg/research/genome-sequencing/tcga bdh2-mediated pro-tumorigenic processes pro-tumorigenic processes mediated debiased inverse-variance weighted wilcoxon rank-sum tests disrupting protein-protein interactions genome-wide profiling identifies article download pdf fine-tune pathway output potentiate anti-tumor responses comprehensive multi-omics analysis low-bdh2-expressing tumors regulate hla-dr expression summary-based mendelian randomization y-axis identifies icd-o-3 diagnostic codes wilcoxon-mann–whitney test small-cell lung cancer met genome-wide significance ras-mapk signaling pathway tumor-infiltrating immune cells hla-dr immune subtypes signature-based drug repositioning low-expression groups based employing ras-mapk inhibitors dna methylation-related genes genome-wide association analysis wilcoxon rank sum ras/mapk pathway activity dna methylation-based signature ras-mapk pathway inhibition ras/raf/mapk pathway transcriptome-wide association study broader tumor-suppressive roles immune-related genes—including immune-related gene features multi-omics analysis multi-omics approaches x-axis displays progeny-based easier package multi-omics analyses inverse variance weighted including tsc/mtor full access high-intensity immunoreactivity observed cell differentiation stage ridge regression models package “grswsci/groundwork” provided utilized rna-seq data
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headline:Identification of novel susceptibility loci for testicular germ cell tumors through multi-omics analysis
description:This study aimed to identify potential susceptibility loci for testicular germ cell tumors (TGCT) through a comprehensive multi-omics analysis. A Mendelian randomization (MR) analysis was conducted to investigate the causal relationships between immune cell phenotypes and TGCT. Summary-based Mendelian Randomization (SMR) and colocalization analyses were subsequently performed to examine candidate phenotypes and TGCT using quantitative trait locis from multiple datasets. Differential gene expression analysis was employed to explore the immune landscape of the target gene in the TGCT tumor microenvironment using UCSC databases. Additionally, potential pathway mechanisms were investigated to elucidate the functional role of candidate genes. MR analysis identified a significant causal association between the immune cell phenotype HLA-DR on monocytes and TGCT (p = 0.02). SMR analysis revealed that BDH2 was significantly associated with TGCT susceptibility (OR = 0.597, p = 2.21e-07). Colocalization analysis suggested shared genetic variation between BDH2 and TGCT (PP.H4 = 0.95). Immunohistochemistry staining confirmed that BDH2 mRNA levels were significantly lower in TGCT tissues than in normal controls (p < 0.001). In the TGCT tumor microenvironment, lower BDH2 expression was associated with higher immune scores, with T cells and B cells predominantly enriched in the low-expression group, whereas monocytes and endothelial cells were more abundant in the high-expression group. Furthermore, members of the HLA family, exhibited significant correlations between their methylation levels and low BDH2 expression groups. Pathway analysis indicated that BDH2 may influence TGCT progression through the RAS-MAPK signaling pathway. Our findings support a significant susceptibility relationship between the phenotype HLA-DR on monocytes, BDH2, and TGCT.
datePublished:2025-06-03T00:00:00Z
dateModified:2025-06-03T00:00:00Z
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keywords:
HLA-DR
BDH2
Testicular germ cell tumors
Mendelian Randomization
Multi-omics analysis
Oncology
Cancer Research
Surgical Oncology
Molecular Medicine
Radiotherapy
Internal Medicine
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headline:Identification of novel susceptibility loci for testicular germ cell tumors through multi-omics analysis
description:This study aimed to identify potential susceptibility loci for testicular germ cell tumors (TGCT) through a comprehensive multi-omics analysis. A Mendelian randomization (MR) analysis was conducted to investigate the causal relationships between immune cell phenotypes and TGCT. Summary-based Mendelian Randomization (SMR) and colocalization analyses were subsequently performed to examine candidate phenotypes and TGCT using quantitative trait locis from multiple datasets. Differential gene expression analysis was employed to explore the immune landscape of the target gene in the TGCT tumor microenvironment using UCSC databases. Additionally, potential pathway mechanisms were investigated to elucidate the functional role of candidate genes. MR analysis identified a significant causal association between the immune cell phenotype HLA-DR on monocytes and TGCT (p = 0.02). SMR analysis revealed that BDH2 was significantly associated with TGCT susceptibility (OR = 0.597, p = 2.21e-07). Colocalization analysis suggested shared genetic variation between BDH2 and TGCT (PP.H4 = 0.95). Immunohistochemistry staining confirmed that BDH2 mRNA levels were significantly lower in TGCT tissues than in normal controls (p < 0.001). In the TGCT tumor microenvironment, lower BDH2 expression was associated with higher immune scores, with T cells and B cells predominantly enriched in the low-expression group, whereas monocytes and endothelial cells were more abundant in the high-expression group. Furthermore, members of the HLA family, exhibited significant correlations between their methylation levels and low BDH2 expression groups. Pathway analysis indicated that BDH2 may influence TGCT progression through the RAS-MAPK signaling pathway. Our findings support a significant susceptibility relationship between the phenotype HLA-DR on monocytes, BDH2, and TGCT.
datePublished:2025-06-03T00:00:00Z
dateModified:2025-06-03T00:00:00Z
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HLA-DR
BDH2
Testicular germ cell tumors
Mendelian Randomization
Multi-omics analysis
Oncology
Cancer Research
Surgical Oncology
Molecular Medicine
Radiotherapy
Internal Medicine
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