Interferon gamma expression and mortality in unselected cohorts of urothelial bladder cancer patients

PLoS One. 2022 Aug 30;17(8):e0271339. doi: 10.1371/journal.pone.0271339. eCollection 2022.

Abstract

Background: The role of interferon gamma (IFN-γ) expression in long-term survival has not been studied in patients with urinary bladder cancer (UBC). IFN-γ expression was characterized among various UBC patient cohorts to assess if IFN-γ status is associated with overall survival (OS).

Methods: A tumor-based IFN-γ gene signature was evaluated among adult UBC patients newly diagnosed between 2004 and 2017 from two hospital systems in New York. Patient cohorts included metastatic (stage IV or progressing to stage IV [MBC]), muscle-invasive (stages T2a to T4a [MIBC]), and non-muscle-invasive (carcinoma in situ or stages 0a, 0is, and I [NMIBC]) disease. Descriptive analyses were conducted comparing IFN-γ signature in the highest tertile to those in the lowest two tertiles.

Results: 234 patients with bladder cancer were evaluated (56 MBC, 38 MIBC, and 140 NMIBC). Median OS was only reached in the MIBC cohort for those with an IFN-γ signature in the lowest two tertiles (15.03 months [95% CI, 8.50-50.60]). Those with an IFN-γ signature in the highest tertile had a decreased risk of mortality in all cohorts indicating better survival, but this was statistically significant in only the MIBC cohort (adjusted HR = 0.09 [95% CI, 0.01-0.73]).

Conclusion: IFN-γ signature status was associated with a decreased mortality risk in all cohorts, particularly MIBC, indicating that it may be a prognostic marker of survival in patients with UBC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carcinoma, Transitional Cell*
  • Cohort Studies
  • Humans
  • Interferon-gamma / genetics
  • Neoplasm Invasiveness
  • New York
  • Prognosis
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Interferon-gamma

Grants and funding

AstraZeneca provided funding to EpidStrategies (formerly EpidStat Institute). Mt. Sinai was a subcontractor of EpidStrategies (formerly EpidStat Institute). The funders were involved in the study design, sample analysis, preparation of the manuscript, and decision to publish. At the time of the analysis, Karma Rabon-Stith, Norah Shire, and Philip Zachary Brohawn received a salary from AstraZeneca.