Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisions
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-mesenc...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1042766/full |
| _version_ | 1826892597477507072 |
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| author | Camila Machado Baldavira Tabatha Gutierrez Prieto Juliana Machado-Rugolo Juliana Machado-Rugolo Jurandir Tomaz de Miranda Lizandre Keren Ramos da Silveira Ana Paula Pereira Velosa Walcy Rosolia Teodoro Alexandre Ab’Saber Teresa Takagaki Vera Luiza Capelozzi |
| author_facet | Camila Machado Baldavira Tabatha Gutierrez Prieto Juliana Machado-Rugolo Juliana Machado-Rugolo Jurandir Tomaz de Miranda Lizandre Keren Ramos da Silveira Ana Paula Pereira Velosa Walcy Rosolia Teodoro Alexandre Ab’Saber Teresa Takagaki Vera Luiza Capelozzi |
| author_sort | Camila Machado Baldavira |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T20:42:32Z |
| format | Article |
| id | doaj.art-8be55e4381aa4e52ad5c3914cd2e488d |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2025-02-17T04:27:37Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-8be55e4381aa4e52ad5c3914cd2e488d2025-01-09T14:19:12ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.10427661042766Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisionsCamila Machado Baldavira0Tabatha Gutierrez Prieto1Juliana Machado-Rugolo2Juliana Machado-Rugolo3Jurandir Tomaz de Miranda4Lizandre Keren Ramos da Silveira5Ana Paula Pereira Velosa6Walcy Rosolia Teodoro7Alexandre Ab’Saber8Teresa Takagaki9Vera Luiza Capelozzi10Department of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, BrazilDepartment of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, BrazilDepartment of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, BrazilHealth Technology Assessment Center, Clinical Hospital, Medical School of São Paulo State University, Botucatu, São Paulo, BrazilRheumatology 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, BrazilRheumatology 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, BrazilRheumatology 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, BrazilRheumatology 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, BrazilDepartment of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, BrazilDivision of Pneumology, Instituto do Coração (Incor), University of São Paulo Medical School (USP), São Paulo, BrazilDepartment of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, BrazilLung 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.1042766/fulllung cancerextracellular matrixepithelial-to-mesenchymal transitionWNT signaling pathwayglycosaminoglycans |
| spellingShingle | Camila Machado Baldavira Tabatha Gutierrez Prieto Juliana Machado-Rugolo Juliana Machado-Rugolo Jurandir Tomaz de Miranda Lizandre Keren Ramos da Silveira Ana Paula Pereira Velosa Walcy Rosolia Teodoro Alexandre Ab’Saber Teresa Takagaki Vera Luiza Capelozzi Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisions Frontiers in Oncology lung cancer extracellular matrix epithelial-to-mesenchymal transition WNT signaling pathway glycosaminoglycans |
| title | Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisions |
| title_full | Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisions |
| title_fullStr | Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisions |
| title_full_unstemmed | Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisions |
| title_short | Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisions |
| title_sort | modeling extracellular matrix through histo molecular gradient in nsclc for clinical decisions |
| topic | lung cancer extracellular matrix epithelial-to-mesenchymal transition WNT signaling pathway glycosaminoglycans |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1042766/full |
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