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Oxidative Stress-regulating Enzymes and Endometrial Cancer Survival in Relation to Metformin Intake in Diabetic

Ewelina Kuusiniemi1,2,3, Peeter Karihtala4, Ulla Puistola5,2,3

  • 1Department of Obstetrics and Gynecology, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, Oulu, Finland; ewelina.kuusiniemi@gmail.com.

Anticancer Research
|November 29, 2023
PubMed
Abstract

Insights

Metformin use in women with type 2 diabetes and endometrial cancer is linked to better survival. Higher manganese superoxide dismutase (MnSOD) levels correlate with improved outcomes in these patients.

Area of Science:

  • Oncology
  • Metabolism
  • Mitochondrial Biology

Background:

  • Metformin influences endometrial cancer by affecting oxidative stress proteins like Nrf2 and Keap1.
  • Manganese superoxide dismutase (MnSOD) is crucial for managing mitochondrial oxidative stress but has complex roles in cancer.
  • Limited data exist on MnSOD's role in endometrial cancer, particularly concerning metformin use.

Purpose of the Study:

  • To investigate the association between mitochondrial redox regulation and endometrial cancer survival.
  • To explore the impact of metformin consumption on this relationship in women with type 2 diabetes mellitus (T2DM).

Main Methods:

  • Retrospective cohort study of 121 endometrial cancer patients with T2DM (2007-2014).
  • 58 patients used metformin at diagnosis.
  • Assessed tumor Nrf2, Keap1 (immunohistochemistry), and MnSOD (immunohistochemistry and serum).

Main Results:

  • High MnSOD tissue expression correlated with better overall survival in metformin users (univariate, p=0.03).
  • High serum MnSOD was linked to better overall survival after adjusting for histology and stage (HR=0.22, p=0.01).
  • No significant association between MnSOD, Nrf2, or Keap1 and survival was observed in non-metformin users.

Conclusions:

  • Elevated MnSOD expression is associated with improved overall survival in endometrial cancer patients with T2DM who are taking metformin.
  • This suggests a potential role for MnSOD as a predictive biomarker in metformin-treated endometrial cancer patients.
Keywords:
Endometrial carcinomaKeap1MnSODNrf2metforminoxidative stresstype 2 diabetes

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