Identification of MDM2 as a prognostic and immunotherapeutic biomarker in a comprehensive pan-cancer analysis: A promising target for breast cancer, bladder cancer and ovarian cancer immunotherapy

Life Sci. 2023 Aug 15:327:121832. doi: 10.1016/j.lfs.2023.121832. Epub 2023 Jun 3.

Abstract

Background: The murine double minute 2 (MDM2) gene is a crucial factor in the development and progression of various cancer types. Multiple rigorous scientific studies have consistently shown its involvement in tumorigenesis and cancer progression in a wide range of cancer types. However, a comprehensive analysis of the role of MDM2 in human cancer has yet to be conducted.

Methods: We used various databases, including TIMER2.0, TCGA, GTEx and STRING, to analyze MDM2 expression and its correlation with clinical outcomes, interacting genes and immune cell infiltration. We also investigated the association of MDM2 with immune checkpoints and performed gene enrichment analysis using DAVID tools.

Results: The pan-cancer MDM2 analysis found that MDM2 expression and mutation status were observably different in 25 types of cancer tissue compared with healthy tissues, and prognosis analysis showed that there was a significant correlation between MDM2 expression and patient prognosis. Furthermore, correlation analysis showed that MDM2 expression was correlated with tumor mutational burden, microsatellite instability and drug sensitivity in certain cancer types. We found that there was an association between MDM2 expression and immune cell infiltration across cancer types, and MDM2 inhibitors might enhance the effect of immunotherapy on breast cancer, bladder cancer and ovarian cancer.

Conclusions: The first systematic pan-cancer analysis of MDM2 was conducted, and it demonstrated that MDM2 was a reliable prognostic biomarker and was closely related to cancer immunity, providing a potential immunotherapeutic target for breast cancer, bladder cancer and ovarian cancer.

Keywords: Biomarker; Immunotherapy; MDM2; Pan-cancer; Prognosis; Survival.

MeSH terms

  • Biomarkers
  • Breast Neoplasms*
  • Female
  • Humans
  • Immunotherapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / therapy
  • Prognosis
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / therapy

Substances

  • Biomarkers
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2