Evidence mapPaperPMID 41528614Full record

ArticleDiscover oncology2026

Mendelian randomization analysis of PKD1 in endometrial cancer and comparative multi-cancer study with renal cell carcinoma.

Xuecheng Pang, Yu Wang, Qiang Zhang, LiJie Gu

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Article in Discover oncology, 2026. 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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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Xuecheng PangGynecology Department 2 of Cangzhou Central Hospital, Cangzhou, 061001, Hebei, China. 18034276663@163.com.
Yu WangGynecology Department 2 of Cangzhou Central Hospital, Cangzhou, 061001, Hebei, China.
Qiang ZhangGynecology Department 2 of Cangzhou Central Hospital, Cangzhou, 061001, Hebei, China.
LiJie GuDepartment of Anesthesiology 2 of Cangzhou Central Hospital, Cangzhou, 061001, Hebei, China.

Funding

Cangzhou Key Research and Development Plan Self funded Project Project 204106119
6 · The paper itself

Abstract

backgroundPolycystic kidney disease 1 (PKD1) has emerged as a potential oncogene in various malignancies, but its causal relationship with endometrial cancer risk and clinical outcomes remains unclear. This study employed Mendelian randomization (MR) analysis to investigate the causal effects of gene expression on endometrial cancer susceptibility, with comparative analysis to renal cell carcinoma, focusing on PKD1’s functional role.

methodsWe conducted a comprehensive summary-data-based Mendelian randomization (SMR) analysis using expression quantitative trait loci (eQTL) from CAGE sparse tissue dataset as instrumental variables. The analysis examined 30 candidate genes for endometrial cancer and 29 genes for renal cancer risk using UK Biobank GWAS data. Cross-cancer comparative analysis identified shared susceptibility genes between both malignancies. PKD1’s role was further characterized through correlation network analysis, immune cell infiltration profiling, and Cox regression survival analysis in 553 endometrial cancer patients. Experimental validation was performed using qRT-PCR in representative cancer cell lines compared to normal controls.

resultsSMR analysis revealed modest but statistically significant causal effects for multiple genes on both cancer types (p_SMR < 0.05), with odds ratios clustering around 1.0. Comparative analysis between renal cancer (220 genes) and endometrial cancer (196 genes) identified only 12 shared susceptibility genes (2.8% overlap) including EP300, CKB, NME7, and TATDN3, highlighting distinct genetic architectures. PKD1 correlation network analysis in endometrial cancer demonstrated positive associations with PET100, AC093899.1, and PDE4DIPP1. Importantly, PKD1 expression levels significantly influenced tumor immune microenvironment composition, with PKD1-low endometrial tumors showing enhanced infiltration of myeloid dendritic cells, T helper cells, and Th1 cells (p < 0.05). However, Cox regression analysis revealed that PKD1 expression did not impact patient survival outcomes (HR = 1.020, 95% CI: 0.681–1.529, p = 0.923), while clinical stage and primary therapy outcome remained significant prognostic factors.

conclusionsThis multi-cancer Mendelian randomization study provides evidence for largely distinct genetic landscapes between renal and endometrial cancers, with minimal gene overlap. PKD1 demonstrates a novel dual role in endometrial cancer pathogenesis.

Indexed as

Endometrial cancerImmune microenvironmentMendelian randomizationPKD1Renal cell carcinoma

Identifiers

PMID41528614
PMCPMC12886693

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.