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Updated: Jul 10, 2026
Analyzing Tumor Gene Expression Factors with the CorExplorer Web Portal
Published on: October 11, 2019
Interleukin-2 transcriptomic expression correlates with prolonged survival and with GNAS alterations in patients with
J Ahmed1, D Nishizaki2, Y Fujiwara3
1Developmental Therapeutics Clinic, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institute of Health, Bethesda, USA.
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:
Among 514 patients, 14.6% had high IL-2 RNA expression (≥75th percentile) and 35% had less than first percentile IL-2 expression. IL-2 expression (greater than or equal to first percentile RNA rank) significantly/independently correlated with high expression of immune checkpoints (TIM-3, BTLA), IL-2Rγ subunits, and ERBB2, GNAS, and NF1 aberrations. Increasing IL-2 RNA expression (multivariable linear regression) correlated with increasing likelihood of GNAS alterations (P = 0.02). GNASR201C-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:
High IL-2 tissue transcript levels correlated with better outcome in advanced cancer patients and those with GNAS alterations; the latter finding was confirmed by increased IL-2 production by CRISPR-edited GNASR201C cells, suggesting a functional interaction between this mutation and IL-2.
