Extracellular matrix profiles determine risk and prognosis of the squamous cell carcinoma subtype of non-small cell lung carcinoma
Year: 2022
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Squamous cell carcinoma (SqCC) is a subtype of non-small cell lung cancer for which patient prognosis remains poor. The extracellular matrix (ECM) is critical in regulating cell behavior; however, its importance in tumor aggressiveness remains to be comprehensively characterized. METHODS: Multi-omics data of SqCC human tumor specimens was combined to characterize ECM features associated with initiation and recurrence. Penalized logistic regression was used to define a matrix risk signature for SqCC tumors and its performance across a panel of tumor types and in SqCC premalignant lesions was evaluated. Consensus clustering was used to define prognostic matreotypes for SqCC tumors. Matreotype-specific tumor biology was defined by integration of bulk RNAseq with scRNAseq data, cell type deconvolution, analysis of ligand-receptor interactions and enriched biological pathways, and through cross comparison of matreotype expression profiles with aging and idiopathic pulmonary fibrosis lung profiles. RESULTS: This analysis revealed subtype-specific ECM signatures associated with tumor initiation that were predictive of premalignant progression. We identified an ECM-enriched tumor subtype associated with the poorest prognosis. In silico analysis indicates that matrix remodeling programs differentially activate intracellular signaling in tumor and stromal cells to reinforce matrix remodeling associated with resistance and progression. The matrix subtype with the poorest prognosis resembles ECM remodeling in idiopathic pulmonary fibrosis and may represent a field of cancerization associated with elevated cancer risk. CONCLUSIONS: Collectively, this analysis defines matrix-driven features of poor prognosis to inform precision medicine prevention and treatment strategies towards improving SqCC patient outcome.
Source: Genome Medicine
Institutions: Garvan Institute of Medical Research, UNSW Sydney, The Kinghorn Cancer Centre, National Cancer Institute, Center for Cancer Research, MiNA Therapeutics Limited (United Kingdom), The University of Sydney, Royal Prince Alfred Hospital, NSW Health Pathology, Western Sydney University, Woolcock Institute of Medical Research
Language: English
Topic: Lung Cancer Research Studies
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,480
Awards: The collagen-rich matrix as a driver of breast cancer progression and resistance to therapy, G1807718159, G391337325, Delving deeper into the Matrix: Redefining the Extracellular Matrix in Cancer Treatment, G4488796276, Transient tissue ‘priming’ via FAK inhibition to impair pancreatic cancer progression and improve sensitivity to gemcitabine/Abraxane, G6104419216, Reversing the biomechanical dysregulation of cancer cell signalling to improve targeted therapies, G8220982166
OpenAlex ID: W4309440909