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

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. 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.