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Sodium-Glucose Cotransporter 2 (SGLT2) as a Potential Biomarker and Target in Papillary Renal Cell Carcinoma

Erman Akkus1, Emre Yekedüz2, Yüksel Ürün1

  • 1Department of Medical Oncology, Ankara University Faculty of Medicine, Ankara, Türkiye; Cancer Research Institute, Ankara University, Ankara, Türkiye.

Clinical Genitourinary Cancer
|February 28, 2025
PubMed
Abstract

Insights

This study suggests Sodium-glucose cotransporter 2 (SGLT2) may play a role in papillary renal cell carcinoma (pRCC). SGLT2 expression is linked to poorer survival, indicating its potential as a biomarker for pRCC.

Area of Science:

  • Oncology
  • Nephrology
  • Molecular Biology

Background:

  • Sodium-glucose cotransporter 2 (SGLT2) is crucial in kidney function and its inhibitors are used for diabetes, heart failure, and kidney disease.
  • The role of SGLT2 in papillary renal cell carcinoma (pRCC) remains unexplored.

Purpose of the Study:

  • To investigate the expression of SGLT2 in pRCC.
  • To analyze the correlation between SGLT2 expression and clinical-molecular features.
  • To determine the prognostic significance of SGLT2 in pRCC patient survival.

Main Methods:

  • Utilized The Cancer Genome Atlas Program and Gene Expression Omnibus datasets.
  • Analyzed SGLT2 mRNA expression z-scores in pRCC tumors compared to normal samples.
  • Correlated SGLT2 expression with gene expression, tumor mutational burden, aneuploidy, and overall survival (OS).

Main Results:

  • SGLT2 expression was low in 66% of 273 pRCC patients.
  • High correlation observed between SGLT2 and genes like IRX5, FOXC1, and HIF-2α.
  • SETD2 alterations were more frequent in the unaltered SGLT2 expression group.
  • SGLT2 expression was a significant independent prognostic factor for OS (HR: 2.446, P = .014).

Conclusions:

  • SGLT2 may function as a pathogenic factor in pRCC.
  • SGLT2 expression could serve as a potential biomarker for pRCC.
  • Further mechanistic studies are required to confirm these findings.
Keywords:
PapillaryRenal cell carcinomaSGLT2SLC5A2Sodium-glucose cotransporter 2

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