Portal de investigação
Proteomic Identification of a Gastric Tumor ECM Signature Associated With Cancer Progression
Data de publicação:
Autores da FMUP
Participantes de fora da FMUP
- Moreira, AM
- Ferreira, RM
- Carneiro, P
- Osório, H
- Barbosa, J
- Preto, J
- Pinto-do-O, P
- Seruca, R
Unidades de investigação
Abstract
The extracellular matrix (ECM) plays an undisputable role in tissue homeostasis and its deregulation leads to altered mechanical and biochemical cues that impact cancer development and progression. Herein, we undertook a novel approach to address the role of gastric ECM in tumorigenesis, which remained largely unexplored. By combining decellularization techniques with a high-throughput quantitative proteomics approach, we have performed an extensive characterization of human gastric mucosa, uncovering its composition and distribution among tumor, normal adjacent and normal distant mucosa. Our results revealed a common ECM signature composed of 142 proteins and indicated that gastric carcinogenesis encompasses ECM remodeling through alterations in the abundance of 24 components, mainly basement membrane proteins. Indeed, we could only identify one de novo tumor-specific protein, the collagen alpha-1(X) chain (COL10A1). Functional analysis of the data demonstrated that gastric ECM remodeling favors tumor progression by activating ECM receptors and cellular processes involved in angiogenesis and cell-extrinsic metabolic regulation. By analyzing mRNA expression in an independent GC cohort available at the TGCA, we validated the expression profile of 12 differentially expressed ECM proteins. Importantly, the expression of COL1A2, LOX and LTBP2 significantly correlated with high tumor stage, with LOX and LTBP2 further impacting patient overall survival. These findings contribute for a better understanding of GC biology and highlight the role of core ECM components in gastric carcinogenesis and their clinical relevance as biomarkers of disease prognosis.
Dados da publicação
- ISSN/ISSNe:
- 2296-889X, 2296-889X
- Tipo:
- Article
- Páginas:
- -
- Link para outro recurso:
- www.scopus.com
Frontiers in Molecular Biosciences Frontiers Media S.A.
Citações Recebidas na Web of Science: 5
Citações Recebidas na Scopus: 13
Documentos
- Não há documentos
Filiações
Keywords
- extracellular matrix (ECM); gastric cancer; matrisome; biomarker; proteomics
Proyectos asociados
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Investigador Principal: Maria de Fátima Machado Henriques Carneiro
Estudo Clínico Académico . 2021
Gastric Cancer Morphological, Immunophenotypic and molecular heterogeneity
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Estudo Clínico Académico . 2020
Citar a publicação
Moreira AM,Ferreira RM,Carneiro P,Figueiredo J,Osório H,Barbosa J,Preto J,Pinto P,Carneiro F,Seruca R. Proteomic Identification of a Gastric Tumor ECM Signature Associated With Cancer Progression. Front. Mol. Biosci. 2022. 9. 818552. IF:5,000. (2).
