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Explore the potential mechanisms between ertugliflozin and kidney cancer through bioinformatics analysis and Mendelian randomization study - PubMed

3 days ago
  • #Mendelian-randomization
  • #kidney-cancer
  • #ertugliflozin
  • Study explores the potential link between ertugliflozin (an SGLT2 inhibitor) and kidney cancer using bioinformatics and Mendelian randomization.
  • Identified 15 core targets linking ertugliflozin and clear cell renal cell carcinoma (ccRCC) through network toxicology.
  • Feature genes SRC and ESR2 were identified via TCGA database analysis, with SLC5A2 showing lower expression in tumor tissues.
  • Mendelian randomization analysis suggests ESR2 may increase ccRCC risk, while SRC shows no association.
  • SGLT2 inhibition is potentially linked to higher renal cell carcinoma risk (OR 3.05, P = 0.04).
  • UK Biobank data shows a strong association between SGLT2 inhibition and ccRCC risk (OR 83.70, P < 0.01).
  • Experimental validation confirms ertugliflozin acts on ESR2, not SRC, suggesting a mechanism for kidney cancer risk.
  • Conclusion: Ertugliflozin may influence kidney cancer via ESR2, and SGLT2 inhibition could contribute to renal cancer risk.