Bidirectional Mendelian Randomization identifies plasma proteins associated with Cervical Cancer risk DOI

Yanhong Zhao,

Qianqian Ruan,

Jinghua Ning

et al.

Published: May 13, 2025

Abstract Background Cervical cancer continues to pose a considerable challenge global health, necessitating innovative approaches for improved diagnostics and personalized treatment strategies. Prior investigations have suggested that plasma proteins may play role in the pathogenesis of cervical cancer; however, these studies do not confirm causal relationship. To address this gap, conducted large-scale Mendelian randomization (MR) study proteome. Methods We two-sample bidirectional analysis 4,907 using publicly available genome-wide association (GWAS) summary statistics investigate relationship between proteome risk. Analytical methods included inverse variance weighting (IVW), weighted median, MR-Egger regression, simple models. Additionally, we performed sensitivity analyses evaluate heterogeneity horizontal pleiotropy through Cochran's Q test, intercept, MR-PRESSO leave-one-out analysis. also applied false discovery rate (FDR) correction results all (IVW) identify most strongly associated with cancer. Finally, enriched relevant protein genes Kyoto Encyclopedia Genes Genomes (KEGG) Gene Ontology (GO) GeneMANIA disease-related pathways. Results According IVW method, seven are significantly risk (FDR-adjusted p < 0.05). Specifically, six demonstrated protective factors: DEFB135 (OR = 0.201, 95% CI 0.082–0.492, p 0.001), FGL2 0.104, 0.032–0.338, FTMT 0.612, 0.465–0.804, PDIA4 0.088, 0.026–0.295, SPHK2 0.102, 0.030–0.350, TMED2 0.045, 0.008–0.246, 0.001). In contrast, RACGAP1 1.755, 1.286–2.395, 0.001) was identified as factor. Reverse MR revealed no significant evidence reverse causation (p > 0.05) proteins. Functional enrichment several biologically pathways potentially involved pathogenesis, including establishment organelle localization, regulation oxidoreductase activity, Ferroptosis, Porphyrin metabolism. Conclusion These findings suggest DEFB135, FGL2, FTMT, PDIA4, SPHK2, protect against cancer, while represent potential The tumor markers provide mechanistic insights into molecular basis warrant further investigation functional studies.

Language: Английский

Bidirectional Mendelian Randomization identifies plasma proteins associated with Cervical Cancer risk DOI

Yanhong Zhao,

Qianqian Ruan,

Jinghua Ning

et al.

Published: May 13, 2025

Abstract Background Cervical cancer continues to pose a considerable challenge global health, necessitating innovative approaches for improved diagnostics and personalized treatment strategies. Prior investigations have suggested that plasma proteins may play role in the pathogenesis of cervical cancer; however, these studies do not confirm causal relationship. To address this gap, conducted large-scale Mendelian randomization (MR) study proteome. Methods We two-sample bidirectional analysis 4,907 using publicly available genome-wide association (GWAS) summary statistics investigate relationship between proteome risk. Analytical methods included inverse variance weighting (IVW), weighted median, MR-Egger regression, simple models. Additionally, we performed sensitivity analyses evaluate heterogeneity horizontal pleiotropy through Cochran's Q test, intercept, MR-PRESSO leave-one-out analysis. also applied false discovery rate (FDR) correction results all (IVW) identify most strongly associated with cancer. Finally, enriched relevant protein genes Kyoto Encyclopedia Genes Genomes (KEGG) Gene Ontology (GO) GeneMANIA disease-related pathways. Results According IVW method, seven are significantly risk (FDR-adjusted p < 0.05). Specifically, six demonstrated protective factors: DEFB135 (OR = 0.201, 95% CI 0.082–0.492, p 0.001), FGL2 0.104, 0.032–0.338, FTMT 0.612, 0.465–0.804, PDIA4 0.088, 0.026–0.295, SPHK2 0.102, 0.030–0.350, TMED2 0.045, 0.008–0.246, 0.001). In contrast, RACGAP1 1.755, 1.286–2.395, 0.001) was identified as factor. Reverse MR revealed no significant evidence reverse causation (p > 0.05) proteins. Functional enrichment several biologically pathways potentially involved pathogenesis, including establishment organelle localization, regulation oxidoreductase activity, Ferroptosis, Porphyrin metabolism. Conclusion These findings suggest DEFB135, FGL2, FTMT, PDIA4, SPHK2, protect against cancer, while represent potential The tumor markers provide mechanistic insights into molecular basis warrant further investigation functional studies.

Language: Английский

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