ArticleJournal of translational medicine2024
Integrating plasma protein-centric multi-omics to identify potential therapeutic targets for pancreatic cancer.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- The Association Between Physical Activity and Domain-Specific Cognitive Function in the Elderly: A Cross-Sectional Study and Genetic Analysis.Brain and behavior · 2026Review
- The association between sarcopenia, sedentary behavior, and the motor cognitive risk syndrome: A Mendelian randomization study.Medicine · 2026Article
- From proteome-wide Mendelian randomization and multi-omics integration to functional validation: TGFB3 as a prioritized candidate in gastric adenocarcinoma.Frontiers in oncology · 2026Article
- Integrative Multi-Omics Mendelian Randomization Identifies BLMH as a Keratinocyte-Enriched Protective Candidate Gene and Potential Therapeutic Target in Psoriasis.Journal of inflammation research · 2026Article
- Article
- Multi-omics Mendelian randomization integrating RNA-seq, eQTL and pQTL data revealed CPXM1 as a potential drug target for osteoporosis.Hereditas · 2025Article
- Identification of novel plasma proteins as promising noninvasive biomarker for early diagnosis and surveillance of pancreatic ductal adenocarcinoma.Journal of gastroenterology · 2025Article
- Integrative Analysis of Plasma Proteome and Genome Reveals Novel Drug Targets for Chronic Rhinosinusitis and Nasal Polyps.World journal of otorhinolaryngology - head and neck surgery · 2025Article
- Mediating Role of the ANGPTL3/TFPI Protein Ratio in Regulating T-Cell Surface Glycoprotein CD5 Levels on Knee Osteoarthritis (KOA): A Mendelian Randomization Study.International journal of molecular sciences · 2025Article
- Identification of Novel Protein Biomarkers for Intrahepatic Cholangiocarcinoma by Integrating Human Plasma Proteome with Genome.Journal of gastrointestinal cancer · 2025Article
- Identification of druggable targets in acute kidney injury by proteome- and transcriptome-wide Mendelian randomization and bioinformatics analysis.Biology direct · 2025Article
- Identification of Brain Cell Type-Specific Therapeutic Targets for Glioma From Genetics.CNS neuroscience & therapeutics · 2024Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
backgroundDeciphering the role of plasma proteins in pancreatic cancer (PC) susceptibility can aid in identifying novel targets for diagnosis and treatment.
methodsWe examined the relationship between genetically determined levels of plasma proteins and PC through a systemic proteome-wide Mendelian randomization (MR) analysis utilizing cis-pQTLs from multiple centers. Rigorous sensitivity analyses, colocalization, reverse MR, replications with varying instrumental variable selections and additional datasets, as well as subsequent meta-analysis, were utilized to confirm the robustness of significant findings. The causative effect of corresponding protein-coding genes' expression and their expression pattern in single-cell types were then investigated. Enrichment analysis, between-protein interaction and causation, knock-out mice models, and mediation analysis with established PC risk factors were applied to indicate the pathogenetic pathways. These candidate targets were ultimately prioritized upon druggability and potential side effects predicted by a phenome-wide MR.
resultsTwenty-one PC-related circulating proteins were identified in the exploratory phase with no evidence for horizontal pleiotropy or reverse causation. Of these, 11 were confirmed in a meta-analysis integrating external validations. The causality at a transcription level was repeated for neutrophil elastase, hydroxyacylglutathione hydrolase, lipase member N, protein disulfide-isomerase A5, xyloside xylosyltransferase 1. The carbohydrate sulfotransferase 11 and histo-blood group ABO system transferase exhibited high-support genetic colocalization evidence and were found to affect PC carcinogenesis partially through modulating body mass index and type 2 diabetes, respectively. Approved drugs have been established for eight candidate targets, which could potentially be repurposed for PC therapies. The phenome-wide investigation revealed 12 proteins associated with 51 non-PC traits, and interference on protein disulfide-isomerase A5 and cystatin-D would increase the risk of other malignancies.
conclusionsBy employing comprehensive methodologies, this study demonstrated a genetic predisposition linking 21 circulating proteins to PC risk. Our findings shed new light on the PC etiology and highlighted potential targets as priorities for future efforts in early diagnosis and therapeutic strategies of PC.
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