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cGAS-STING pathway expression as a prognostic tool in NSCLC

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-leak...

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Autores principales: Raaby Gammelgaard, Kristine, Sandfeld-Paulsen, Birgitte, Godsk, Stine Høvring, Demuth, Christina, Meldgaard, Peter, Sorensen, Boe Sandahl, Jakobsen, Martin Roelsgaard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867790/
https://www.ncbi.nlm.nih.gov/pubmed/33569317
http://dx.doi.org/10.21037/tlcr-20-524
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author Raaby Gammelgaard, Kristine
Sandfeld-Paulsen, Birgitte
Godsk, Stine Høvring
Demuth, Christina
Meldgaard, Peter
Sorensen, Boe Sandahl
Jakobsen, Martin Roelsgaard
author_facet Raaby Gammelgaard, Kristine
Sandfeld-Paulsen, Birgitte
Godsk, Stine Høvring
Demuth, Christina
Meldgaard, Peter
Sorensen, Boe Sandahl
Jakobsen, Martin Roelsgaard
author_sort Raaby Gammelgaard, Kristine
collection PubMed
description 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.
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spelling pubmed-78677902021-02-09 cGAS-STING pathway expression as a prognostic tool in NSCLC Raaby Gammelgaard, Kristine Sandfeld-Paulsen, Birgitte Godsk, Stine Høvring Demuth, Christina Meldgaard, Peter Sorensen, Boe Sandahl Jakobsen, Martin Roelsgaard Transl Lung Cancer Res Original Article 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. AME Publishing Company 2021-01 /pmc/articles/PMC7867790/ /pubmed/33569317 http://dx.doi.org/10.21037/tlcr-20-524 Text en 2021 Translational Lung Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Raaby Gammelgaard, Kristine
Sandfeld-Paulsen, Birgitte
Godsk, Stine Høvring
Demuth, Christina
Meldgaard, Peter
Sorensen, Boe Sandahl
Jakobsen, Martin Roelsgaard
cGAS-STING pathway expression as a prognostic tool in NSCLC
title cGAS-STING pathway expression as a prognostic tool in NSCLC
title_full cGAS-STING pathway expression as a prognostic tool in NSCLC
title_fullStr cGAS-STING pathway expression as a prognostic tool in NSCLC
title_full_unstemmed cGAS-STING pathway expression as a prognostic tool in NSCLC
title_short cGAS-STING pathway expression as a prognostic tool in NSCLC
title_sort cgas-sting pathway expression as a prognostic tool in nsclc
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867790/
https://www.ncbi.nlm.nih.gov/pubmed/33569317
http://dx.doi.org/10.21037/tlcr-20-524
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