cGAS-STING pathway expression as a prognostic tool in NSCLC

Kristine Raaby Gammelgaard; Birgitte Sandfeld-Paulsen; Stine Høvring Godsk; Christina Demuth; Peter Meldgaard; Boe Sandahl Sorensen; Martin Roelsgaard Jakobsen

doi:10.21037/tlcr-20-524

cGAS-STING pathway expression as a prognostic tool in NSCLC

Transl Lung Cancer Res. 2021 Jan;10(1):340-354. doi: 10.21037/tlcr-20-524.

Authors

Kristine Raaby Gammelgaard¹, Birgitte Sandfeld-Paulsen², Stine Høvring Godsk¹, Christina Demuth², Peter Meldgaard³, Boe Sandahl Sorensen², Martin Roelsgaard Jakobsen¹

Affiliations

¹ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
² Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
³ Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.

Abstract

Background: Disease recurrence in localized lung adenocarcinoma is a major obstacle for improving the overall outcome of lung cancer. Thus, better prognostic biomarkers are needed to identify patients at risk. In order to clear cancer, immune detection of tumor cells is of vital importance. DNA-leakage into the cytosol and tumor environment is one important tumor-associated danger signal and cGAS is a pivotal DNA-sensor that detects misplaced DNA and initiates an innate immune response. In this study, we investigate the cGAS-STING-pathway expression in tumor tissue and circulating immune cells from lung adenocarcinoma patients in relation to stage of disease and overall survival (OS).

Methods: Gene expression was measured using target specific droplet digital polymerase chain reaction (ddPCR) assays in a cohort of 80 patients with lung adenocarcinoma and 45 patients suspected of lung cancer, but determined to be cancer-free. The expression values were correlated to stage of disease. For further exploration of stage dependent expression, we used a publicly available gene expression data set to stratify patients by stage and correlate gene expression to OS.

Results: In both tumor tissue and peripheral blood mononuclear cells (PBMCs) from cancer patients, we observed differential expression of cGAS-STING pathway components compared to cancer-free individuals. Furthermore, cGAS-STING pathway expression was elevated in PBMCs from patients with localized disease (stage I and II) compared to patients with metastatic disease (stage III and IV). Survival analysis based on publicly available gene expression data sets demonstrated a superior OS for patients with localized disease and high levels of cGAS, STING and TBK1.

Conclusions: The expression of the cGAS-STING pathway is stage dependent and high expression is correlated with localized adenocarcinoma. For patients with localized disease, high cGAS, STING and TBK1 expression correlated with improved OS and may be a potential biomarker for this patient subgroup.

Keywords: Non-small cell lung cancer (NSCLC); STING; adenocarcinoma; immuno-oncology; innate immune system.