Evidence map›Paper›PMID 39035989›Full record

ArticleFrontiers in pharmacology2024

PTGES2 and RNASET2 identified as novel potential biomarkers and therapeutic targets for basal cell carcinoma: insights from proteome-wide mendelian randomization, colocalization, and MR-PheWAS analyses.

Qiu-Ju Han, Yi-Pan Zhu, Jing Sun, Xin-Yu Ding, Xiuyu Wang, Qiang-Zhe Zhang

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Article in Frontiers in pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

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6citing papers in PubMed
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3 · Its place in the literature

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6 citing papers in PubMed.

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4 · The record

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5 · Who and what money

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6 authors.

Qiu-Ju Han *State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, and the Haihe Laboratory of Cell Ecosystem, Tianjin, China.
Yi-Pan Zhu *State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, and the Haihe Laboratory of Cell Ecosystem, Tianjin, China.
Jing SunState Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, and the Haihe Laboratory of Cell Ecosystem, Tianjin, China.
Xin-Yu DingState Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, and the Haihe Laboratory of Cell Ecosystem, Tianjin, China.
Xiuyu WangDepartment of Neurosurgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.
Qiang-Zhe ZhangState Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, and the Haihe Laboratory of Cell Ecosystem, Tianjin, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Basal cell carcinoma (BCC) is the most common skin cancer, lacking reliable biomarkers or therapeutic targets for effective treatment. Genome-wide association studies (GWAS) can aid in identifying drug targets, repurposing existing drugs, predicting clinical trial side effects, and reclassifying patients in clinical utility. Hence, the present study investigates the association between plasma proteins and skin cancer to identify effective biomarkers and therapeutic targets for BCC. Methods: Proteome-wide mendelian randomization was performed using inverse-variance-weight and Wald Ratio methods, leveraging 1 Mb cis protein quantitative trait loci (cis-pQTLs) in the UK Biobank Pharma Proteomics Project (UKB-PPP) and the deCODE Health Study, to determine the causal relationship between plasma proteins and skin cancer and its subtypes in the FinnGen R10 study and the SAIGE database of Lee lab. Significant association with skin cancer and its subtypes was defined as a false discovery rate (FDR) < 0.05. pQTL to GWAS colocalization analysis was executed using a Bayesian model to evaluate five exclusive hypotheses. Strong colocalization evidence was defined as a posterior probability for shared causal variants (PP.H4) of ≥0.85. Mendelian randomization-Phenome-wide association studies (MR-PheWAS) were used to evaluate potential biomarkers and therapeutic targets for skin cancer and its subtypes within a phenome-wide human disease category. Results: PTGES2, RNASET2, SF3B4, STX8, ENO2, and HS3ST3B1 (besides RNASET2, five other plasma proteins were previously unknown in expression quantitative trait loci (eQTL) and methylation quantitative trait loci (mQTL)) were significantly associated with BCC after FDR correction in the UKB-PPP and deCODE studies. Reverse MR showed no association between BCC and these proteins. PTGES2 and RNASET2 exhibited strong evidence of colocalization with BCC based on a posterior probability PP.H4 >0.92. Furthermore, MR-PheWAS analysis showed that BCC was the most significant phenotype associated with PTGES2 and RNASET2 among 2,408 phenotypes in the FinnGen R10 study. Therefore, PTGES2 and RNASET2 are highlighted as effective biomarkers and therapeutic targets for BCC within the phenome-wide human disease category. Conclusion: The study identifies PTGES2 and RNASET2 plasma proteins as novel, reliable biomarkers and therapeutic targets for BCC, suggesting more effective clinical application strategies for patients.

Indexed as

basal cell carcinomabiomarkerscolocalization analysisdrug targetsMR-pheWASplasma proteinsproteome-wide mendelian randomizationsingle nucleotide polymorphisms

Identifiers

PMID39035989
PMCPMC11257982

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