PU.1 upregulation is linked to improved prognosis in non-small cell lung cancer

Front Immunol. 2025 Aug 15:16:1604237. doi: 10.3389/fimmu.2025.1604237. eCollection 2025.

Abstract

Background: Lung cancer is one of the most common types of cancer, which can currently be cured only partially. Even though the function of the transcription factor PU.1 as an oncogene has already been investigated in detail in various studies, its precise function and regulatory mechanisms in non-small cell lung cancer (NSCLC) remain to be fully elucidated.

Methods: Patients with NSCLC and healthy controls were recruited at the Department of Thoracic Surgery of the University Hospital Erlangen. Tissue samples were dissected from patients who underwent lung tumor surgery and blood samples were collected from all participants.

Results: In this study, we showed that the expression of PU.1 was increased both in the blood and in the tumor region of the lung of patients with NSCLC. On a more detailed analysis, PU.1 was found increased the most in CD56dim natural killer cells (NK cells). Furthermore, we demonstrated an increased cytotoxic potential for PU.1 expressing cells as well as improved overall and recurrence-free survival for patients with a higher expression of PU.1, suggesting a beneficial role for PU.1 in NSCLC.

Conclusion: High expression of PU.1 associated with NK cells could lead to a beneficial outcome and survival of NSCLC patients.

Keywords: NK cells; PU.1; metastasis free survival (MFS); non-small cell lung cancer; recurrence free survival (RFS).

MeSH terms

  • Aged
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / immunology
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / immunology
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Protein Spi-1
  • Proto-Oncogene Proteins* / genetics
  • Proto-Oncogene Proteins* / metabolism
  • Trans-Activators* / genetics
  • Trans-Activators* / metabolism
  • Up-Regulation

Substances

  • Proto-Oncogene Proteins
  • Trans-Activators
  • Biomarkers, Tumor
  • Proto-Oncogene Protein Spi-1