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

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dc.contributor.authorBaldavira, Camila Machado
dc.contributor.authorPrieto, Tabatha Gutierrez
dc.contributor.authorMachado-Rugolo, Juliana [UNESP]
dc.contributor.authorde Miranda, Jurandir Tomaz
dc.contributor.authorde Oliveira, Lizandre Keren Ramos
dc.contributor.authorVelosa, Ana Paula Pereira
dc.contributor.authorTeodoro, Walcy Rosolia
dc.contributor.authorAb’Saber, Alexandre
dc.contributor.authorTakagaki, Teresa
dc.contributor.authorCapelozzi, Vera Luiza
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.date.accessioned2023-07-29T13:59:49Z
dc.date.available2023-07-29T13:59:49Z
dc.date.issued2022-11-14
dc.description.abstractLung 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.en
dc.description.affiliationDepartment of Pathology Faculty of Medicine University of São Paulo
dc.description.affiliationHealth Technology Assessment Center Clinical Hospital Medical School of São Paulo State University, São Paulo
dc.description.affiliationRheumatology Division of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Faculty of Medicine University of São Paulo, SP
dc.description.affiliationDivision of Pneumology Instituto do Coração (Incor) University of São Paulo Medical School (USP)
dc.description.affiliationUnespHealth Technology Assessment Center Clinical Hospital Medical School of São Paulo State University, São Paulo
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.identifierhttp://dx.doi.org/10.3389/fonc.2022.1042766
dc.identifier.citationFrontiers in Oncology, v. 12.
dc.identifier.doi10.3389/fonc.2022.1042766
dc.identifier.issn2234-943X
dc.identifier.scopus2-s2.0-85142797732
dc.identifier.urihttp://hdl.handle.net/11449/249006
dc.language.isoeng
dc.relation.ispartofFrontiers in Oncology
dc.sourceScopus
dc.subjectepithelial-to-mesenchymal transition
dc.subjectextracellular matrix
dc.subjectglycosaminoglycans
dc.subjectlung cancer
dc.subjectWNT signaling pathway
dc.titleModeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisionsen
dc.typeArtigo

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