ArticleDiscover oncology2025
Identification of biomarkers for chronic lymphocytic leukemia risk: a proteome-wide Mendelian randomization study.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundChronic lymphocytic leukemia (CLL) is a common hematologic malignancy. Although previous research has explored associations between plasma proteins and CLL, the causal relationships remain unclear. This study used Mendelian randomization (MR) to investigate the causal relationship between 7156 plasma proteins and CLL risk.
methodsA two-sample MR analysis assessed the impact of specific plasma proteins on CLL risk, using data from the Finngen Proteomics project (analyzing 828 participants) and the UK Biobank. Additional analyses included colocalization, phenomenon-wide MR, and protein-protein interaction networks.
resultsThe study identified nine plasma proteins significantly associated with CLL risk. Increased levels of Peptidyl-prolyl cis-trans isomerase E (PPIE) (OR = 1.66, 95% CI 1.22-2.27, P = 0.001) were associated with an increased risk of developing CLL, whereas Protein O-Mannosyltransferase 2 (POMGNT2) (OR = 0.62, 95% CI 0.41-0.91, P = 0.017) and C-C Motif Chemokine Ligand 14(CCL14) (OR = 0.80, 95% CI 0.67-0.94, P = 0.010) were associated with a reduced risk of CLL. Colocalization analysis suggested that PPIE may share pathogenic variants with CLL (PP.H4 = 0.758). Phenomenon-wide MR analysis of PPIE also indicated associations with other clinical features, including rheumatic diseases and type 2 diabetes. Protein-protein interaction and drug-gene interaction analyses highlighted CDC5L and SNW1 as potential therapeutic targets.
conclusionThis study identifies nine plasma proteins linked to CLL risk, with PPIE offering new insights into the disease's pathogenesis. Further research is needed to validate these findings and explore their potential as therapeutic targets.
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