Camila Machado Baldavira , Tabatha Gutierrez Prieto , Maria Luiza Fernezlian de Souza , Aline Nery Qualiotto , Ana Paula Pereira Velosa , Walcy Rosolia Teodoro , Teresa Takagaki , Alexandre Ab'Saber , Vera Luiza Capelozzi
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引用次数: 0
Abstract
Introduction
Non-small cell lung carcinoma (NSCLC), comprising adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), is characterized by an active desmoplastic stroma with an accumulation of extracellular matrix (ECM) proteins. ECM remodeling is a key feature of cancer progression, but the identification of specific therapeutic targets within this compartment remains challenging. Recent studies suggest a link between increased desmoplastic stroma and malignancy in NSCLC, the role of ECM proteins in disease pathogenesis remains unclear.
Methods
We analyzed an exploratory cohort of Pan-Cancer Atlas and a study cohort to identify differentially expressed ECM proteins. Our focus was on fibrillar components (elastin, fibrillin, collagens), glycosaminoglycans (chondroitin sulfate and heparan sulfate), and matricellular proteins (SPARC). Bioinformatics analysis highlighted matrix proteins that modulate ECM functionality and structure, potentially serving as biomarkers and/or therapeutic targets.
Results
Adenocarcinomas exhibited an ECM enriched with abnormal elastin, chondroitin sulfate, and SPARC. Collagen IV expression in the basement membrane was reduced, while collagen III and V were prominent around tumors. LUSC showed more fibrotic ECM, leading to a stiffer microenvironment. While LUSC's basement membrane may be fragmented, it often retains more intact collagen IV compared to LUAD. High elastin expression in LUAD correlated with smaller tumors (P = 0.022), while fibrillin-2 expression was linked to T1 stage (P = 0.035) and pathological stage I (P = 0.014). In LUSC, elastin expression correlated with negative lymph nodes (P = 0.037). SPARC was an independent factor for overall survival for both subtypes (P < 0.05).
Conclusion
This study provides insights into matrix changes in NSCLC and identifies promising candidates for targeted therapies.
期刊介绍：
BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.
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