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Title: Loss of STING expression is prognostic in non-small cell lung cancer.
Austin Authors: Lohinai, Zoltan;Dora, David;Caldwell, Charles;Rivard, Christopher J;Suda, Kenichi;Yu, Hui;Rivalland, Gareth;Ellison, Kim;Rozeboom, Leslie;Dziadziuszko, Rafal;Mitchell, Paul L R ;John, Thomas ;Millan, Inigo S;Ren, Shengxiang;Hirsch, Fred R
Affiliation: Olivia Newton-John Cancer Wellness and Research Centre
Department of Human Physiology and Nutrition, University of Colorado, Colorado Springs, Colorado, USA
Department of Anatomy, Histology, and Embryology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
Departments of Medicine and Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
Division of Thoracic Surgery, Department of Surgery, Faculty of Medicine, Kindai University, Osaka, Japan
Departments of Medicine and Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland
Department of Medicine, Metabolism, and Diabetes, University of Colorado School of Medicine, Aurora, CO, USA
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
Tisch Cancer Institute, Center for Thoracic Oncology, Mount Sinai Health System, New York, New York, USA
National Korányi Institute of Pulmonology, Budapest, Hungary
Issue Date: May-2022
Date: 2022-01-31
Publication information: Journal of Surgical Oncology 2022; 125(6): 1042-1052
Abstract: 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. 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. 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. STING is ubiquitously expressed in NSCLC and associated with T cell function genes, AC histology, EGFR, and KRAS mutations and improved overall survival.
DOI: 10.1002/jso.26804
ORCID: 0000-0002-2975-5701
Journal: Journal of Surgical Oncology
PubMed URL: 35099823
PubMed URL:
Type: Journal Article
Subjects: STING
T cell function genes
non-small cell lung cancer (NSCLC)
Appears in Collections:Journal articles

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