Multilevel Transcriptomic Association Analysis Reveals Key Genes and Potential Mechanisms in Endometrial, Ovarian,...

Area of Science:

• Genomics
• Oncology
• Molecular Biology

Background:

• Endometrial cancer (EC), ovarian cancer (OC), and cervical cancer (CC) are significant gynecological malignancies with complex genetic underpinnings.
• Identifying shared genetic factors and key genes is crucial for understanding their development and for potential therapeutic strategies.

Purpose of the Study:

• To investigate genetic associations for EC, OC, and CC.
• To identify key genes involved in gynecological cancer development using integrated genomic approaches.
• To analyze the functional roles and expression patterns of identified genes.

Main Methods:

• Integration of genome-wide association study (GWAS) data with blood eQTL data.
• Application of S-PrediXcan, SMR, and mBAT-combo for gene association analysis.
• Utilized RNA sequencing for gene expression analysis and functional enrichment studies.

Main Results:

• Identified 690, 620, and 624 genes associated with OC, CC, and EC, respectively.
• Discovered 79, 59, and 61 consistently significant genes across all three methods, highlighting their critical roles.
• Found SPX gene negatively associated with all three cancers, suggesting a potential protective role; 26 key genes showed differential expression in tumor versus normal tissues.

Conclusions:

• A set of key genes associated with EC, OC, and CC has been identified.
• The gene SPX may possess a protective effect against gynecological cancer development.
• Integrated genetic and transcriptomic analyses offer novel insights into molecular mechanisms and potential biomarkers for precision medicine in gynecological malignancies.