Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisions.

Autor:	Baldavira CM; Department of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil., Prieto TG; Department of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil., Machado-Rugolo J; Department of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.; Health Technology Assessment Center, Clinical Hospital, Medical School of São Paulo State University, Botucatu, São Paulo, Brazil., de Miranda JT; Rheumatology Division of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil., de Oliveira LKR; Rheumatology Division of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil., Velosa APP; Rheumatology Division of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil., Teodoro WR; Rheumatology Division of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil., Ab'Saber A; Department of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil., Takagaki T; Division of Pneumology, Instituto do Coração (Incor), University of São Paulo Medical School (USP), São Paulo, Brazil., Capelozzi VL; Department of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 Nov 14; Vol. 12, pp. 1042766. Date of Electronic Publication: 2022 Nov 14 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.1042766
Abstrakt:	Lung cancer still represents a global health problem, being the main type of tumor responsible for cancer deaths. In this context, the tumor microenvironment, and the extracellular matrix (ECM) pose as extremely relevant. Thus, this study aimed to explore the prognostic value of epithelial-to-mesenchymal transition (EMT), Wnt signaling, and ECM proteins expression in patients with non-small-cell lung carcinoma (NSCLC) with clinical stages I-IIIA. For that, we used 120 tissue sections from patients and evaluated the immunohistochemical, immunofluorescence, and transmission electron microscopy (TEM) to each of these markers. We also used in silico analysis to validate our data. We found a strong expression of E-cadherin and β-catenin, which reflects the differential ECM invasion process. Therefore, we also noticed a strong expression of chondroitin sulfate (CS) and collagens III and V. This suggests that, after EMT, the basal membrane (BM) enhanced the motility of invasive cells. EMT proteins were directly associated with WNT5A, and collagens III and V, which suggests that the WNT pathway drives them. On the other hand, heparan sulfate (HS) was associated with WNT3A and SPARC, while WNT1 was associated with CS. Interestingly, the association between WNT1 and Col IV suggested negative feedback of WNT1 along the BM. In our cohort, WNT3A, WNT5A, heparan sulfate and SPARC played an important role in the Cox regression model, influencing the overall survival (OS) of patients, be it directly or indirectly, with the SPARC expression stratifying the OS into two groups: 97 months for high expression; and 65 for low expression. In conclusion, the present study identified a set of proteins that may play a significant role in predicting the prognosis of NSCLC patients with clinical stages I-IIIA. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Baldavira, Prieto, Machado-Rugolo, de Miranda, de Oliveira, Velosa, Teodoro, Ab’Saber, Takagaki and Capelozzi.)
Databáze:	MEDLINE
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