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June 12, 2026ESMO Open0 citationsOpen Access

Interleukin-2 transcriptomic expression correlates with prolonged survival and with GNAS alterations in patients with advanced cancers

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JAJibran AhmedDND. NishizakiYFYu Fujiwara

Key Points

  • This research aims to explore the relationship between interleukin-2 expression and survival outcomes in patients with advanced cancers, particularly relating to GNAS mutations.
  • IL-2 RNA expression was analyzed using databases including OmniSeq and TCGA.
  • Patients from the UCSD cohort (n = 489) were studied for overall survival correlation with IL-2 levels.
  • CRISPR-Cas9-engineered GNAS-mutant cell lines were used to measure IL-2 levels.
  • Higher IL-2 expression was found in GNAS-mutant cell lines compared to controls.
  • IL-2 expression was an independent positive prognostic factor for overall survival (HR 0.74, 95% CI 0.57-0.96, P = 0.02) in UCSD patients.
  • A significant correlation was observed between IL-2 levels and longer overall survival in the TCGA cohort (HR 0.84, 95% CI 0.79-0.91, P < 0.001).

Abstract

BACKGROUND: Interleukin-2 (IL-2) is a critical immunoregulatory molecule. IL-2 RNA expression and correlation with immune markers, gene alterations, and outcomes were analyzed in advanced/metastatic cancers. PATIENTS AND METHODS: We investigated IL-2 transcript data through the OmniSeq clinical-grade laboratory https://www.omniseq.com/; University of California San Diego (UCSD) cohort and The Cancer Genome Atlas (TCGA, https://www.cancer.gov/tcga) databases. UCSD cohort transcriptomic patterns were relativized against a reference population (n = 735) and expressed as percentiles. IL-2 levels were measured by enzyme-linked immunosorbent assay in CRISPR-Cas9-engineered GNAS-mutant Caco-2 cell lines. RESULTS: -mutated (CRISPR) cell lines showed significantly higher levels of IL-2 than controls. IL-2 expression was an independent positive prognostic factor for overall survival (OS) n = 489 UCSD patients with clinical data, hazard ratio (HR) 0.74, 95% confidence interval (CI) 0.57-0.96, P = 0.02, multivariable and significantly correlated with longer OS in TCGA cohort (n = 9869, HR 0.84, 95% CI 0.79-0.91, P < 0.001). CONCLUSIONS: cells, suggesting a functional interaction between this mutation and IL-2.

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Cite This Study

Ahmed et al. (2026) studied this question.

synapsesocial.com/papers/6a2ba18c8101cf8926f00ddehttps://doi.org/10.1016/j.esmoop.2026.107768
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