Loss of STING expression is prognostic in non-small cell lung cancer.

ABSTRACT

BACKGROUND: Stimulator of interferon (IFN) genes (STING) is a protein that promotes type I IFN production essential for T-cell activation. In this study, we aim to characterize STING expression comprehensively using The Cancer Genome Atlas (TCGA) database, cell lines, and patient tumor samples stained with immunohistochemistry. METHODS: Two cohorts were evaluated comprising 721 non-small cell lung cancer (NSCLC) patients and 55 NSCLC cell lines for STING and cyclic GMP-AMP synthase (cGAS) expression using immunohistochemistry. Moreover, an independent cohort of n = 499 patients from the TCGA database was analyzed. Methylation was evaluated on STING and cGAS in five STING-negative NSCLC cell lines. RESULTS: STING RNA expression positively correlates with T cell function and development genes, negatively correlates with cell proliferation and associated with increased survival (5-year-overall survival [OS] 47.3% vs. 38.8%, p = 0.033). STING protein expression is significantly higher in adenocarcinoma (AC) and is lost with increasing stages of AC. STING-positivity is significantly higher in mutant EGFR and KRAS tumors. STING-positive NSCLC patients identified with immunohistochemistry (H-score > 50) have increased survival (median OS 58 vs. 35 months, p = 0.02). Treatment of STING-negative cell lines with a demethylating agent restores STING expression. CONCLUSIONS: STING is ubiquitously expressed in NSCLC and associated with T cell function genes, AC histology, EGFR, and KRAS mutations and improved overall survival.