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. 2025 Jul 1;16(1):1249.
doi: 10.1007/s12672-025-03043-8.

Integrated eQTL-pQTL Mendelian randomization and single-cell sequencing reveal therapeutic targets in ovarian clear cell cancer

Yuwen Qi #  1   2   3 , Yang Gao #  1   2   3 , Hongbing Cai  4   5   6
Affiliations

Integrated eQTL-pQTL Mendelian randomization and single-cell sequencing reveal therapeutic targets in ovarian clear cell cancer

Yuwen Qi et al. Discov Oncol. .

Abstract

Background: Ovarian clear cell cancer (OCCC) is a pathological type of ovarian cancer. OCCC responds poorly to platinum-based chemotherapy drugs and immunotherapy. Currently, there is a lack of targeted drugs for OCCC. It is very urgent to find new therapeutic targets for OCCC.

Methods: We used data from the eQTLGen consortium and deCODE, combined with large Genome-Wide Association Study (GWAS) cohort data, to perform drug target Mendelian randomization (MR) analysis. Colocalization analysis was used to identify target genes. Then, we analyzed single-cell sequencing data from the GEO database, combing with gene enrichment analysis to explore possible molecular mechanisms. Drug screening and molecular docking verified the medicinal value of the targets.

Results: Three genes were selected in the MR analysis. Colocalization supported two of them, PPP1R14A and PTGS2. Single-cell sequencing analysis showed that these genes were related to tumor immunity. Drug prediction and molecular docking showed that PTGS2 had druggable potential.

Conclusions: This study identified two potential drug targets for OCCC. These drug targets may be relevant to tumor immunotherapy. However, further studies are necessary to confirm these findings and clarify the underlying mechanisms.

Keywords: Cancer immunotherapy; Mendelian randomization; Ovarian clear cell cancer; Single-cell RNA sequencing; Therapeutic targets.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Clinical trial number: Not applicable.

Figures

Fig. 1
Fig. 1
Overview of the study design
Fig. 2
Fig. 2
Volcano plot of genes
Fig. 3
Fig. 3
PQTL Mendelian randomization
Fig. 4
Fig. 4
Sensitivity analyses of Mendelian randomization results for pQTL
Fig. 5
Fig. 5
Co-localization analysis of eQTL and GWAS signals for key genes
Fig. 6
Fig. 6
Key gene function enrichment analysis by GO and KEGG
Fig. 7
Fig. 7
Single cell data annotation. A Cell clustering after UMAP. B Four cell annotations. C Bubble chart of 4 classic cell markers. D Cell ratio bar graph corresponding to the sample
Fig. 8
Fig. 8
Expression of key genes in different cell types and enrichment of functional pathways
Fig. 9
Fig. 9
Key genes-related transcriptional regulatory networks, drug screening, and molecular docking of potential compounds
See this image and copyright information in PMC

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