Cancer-associated fibroblasts in early-stage lung adenocarcinoma correlate with tumor aggressiveness.

Autor: Vasiukov G; Department of Biomedical Engineering, School of Engineering, Vanderbilt University, Nashville, TN, USA., Zou Y; Division of Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Senosain MF; Division of Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Rahman JSM; Division of Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Antic S; Division of Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Young KM; Department of Biomedical Engineering, School of Engineering, Vanderbilt University, Nashville, TN, USA., Grogan EL; Division of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA., Kammer MN; Division of Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Maldonado F; Division of Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Reinhart-King CA; Department of Biomedical Engineering, School of Engineering, Vanderbilt University, Nashville, TN, USA. cynthia.reinhart-king@vanderbilt.edu., Massion PP; Division of Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Oct 17; Vol. 13 (1), pp. 17604. Date of Electronic Publication: 2023 Oct 17.
DOI: 10.1038/s41598-023-43296-3
Abstrakt: Lung adenocarcinoma (LUAD) is the predominant type of lung cancer in the U.S. and exhibits a broad variety of behaviors ranging from indolent to aggressive. Identification of the biological determinants of LUAD behavior at early stages can improve existing diagnostic and treatment strategies. Extracellular matrix (ECM) remodeling and cancer-associated fibroblasts play a crucial role in the regulation of cancer aggressiveness and there is a growing need to investigate their role in the determination of LUAD behavior at early stages. We analyzed tissue samples isolated from patients with LUAD at early stages and used imaging-based biomarkers to predict LUAD behavior. Single-cell RNA sequencing and histological assessment showed that aggressive LUADs are characterized by a decreased number of ADH1B + CAFs in comparison to indolent tumors. ADH1B + CAF enrichment is associated with distinct ECM and immune cell signatures in early-stage LUADs. Also, we found a positive correlation between the gene expression of ADH1B + CAF markers in early-stage LUADs and better survival. We performed TCGA dataset analysis to validate our findings. Identified associations can be used for the development of the predictive model of LUAD aggressiveness and novel therapeutic approaches.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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