INVESTIGACION Y DESARROLLO DE NUEVAS ESTRATEGIAS PARA LA DETECCION PRECOZ Y LA PREVENCIÓN DEL CANCER GASTRICO EN LA POBLACIÓN ESPAÑOLA: PROYECTO EPIGASTRIC / EDGAR

PI21/00333

Nombre agencia financiadora Instituto de Salud Carlos III
Acrónimo agencia financiadora ISCIII
Programa Programa Estatal de Generación de Conocimiento y Fortalecimiento del Sistema Español de I+D+I
Subprograma Subprograma Estatal de Generación de Conocimiento
Convocatoria Proyectos de investigación en salud
Año convocatoria 2021
Unidad de gestión Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)
Centro beneficiario INSTITUTO DE INVESTIGACIONES BIOMEDICAS AUGUST PI I SUNYER (IDIBAPS)
Centro realización INSTITUTO DE INVESTIGACIONES BIOMEDICAS AUGUST PI I SUNYER (IDIBAPS)
Identificador persistente https://doi.org/10.13039/501100004587

Publicaciones

Found(s) 2 result(s)
Found(s) 1 page(s)

CTNND1 is involved in germline predisposition to early-onset gastric cancer by affecting cell-to-cell interactions

Zaguán. Repositorio Digital de la Universidad de Zaragoza
  • Herrera-Pariente, Cristina
  • Bonjoch, Laia
  • Muñoz, Jenifer
  • Fernàndez, Guerau
  • Soares de Lima, Yasmin
  • Mahmood, Romesa
  • Cuatrecasas, Miriam
  • Ocaña, Teresa
  • Lopez-Prades, Sandra
  • Llargués-Sistac, Gemma
  • Domínguez-Rovira, Xavier
  • Llach, Joan
  • Luzko, Irina
  • Díaz-Gay, Marcos
  • Lazaro, Conxi
  • Brunet, Joan
  • Castillo-Manzano, Carmen
  • García-González, María Asunción
  • Lanas, Ángel
  • Carrillo, Marta
  • Hernández San Gil, Raquel
  • Quintero, Enrique
  • Sala, Nuria
  • Llort, Gemma
  • Aguilera, Lara
  • Carot, Laura
  • Diez-Redondo, Pilar
  • Jover, Rodrigo
  • Ramon y Cajal, Teresa
  • Cubiella, Joaquín
  • Castells, Antoni
  • Balaguer, Francesc
  • Bujanda, Luis
  • Castellví-Bel, Sergi
  • Moreira, Leticia
Background: CDH1 and CTNNA1 remain as the main genes for hereditary gastric cancer. However, they only explain a small fraction of gastric cancer cases with suspected inherited basis. In this study, we aimed to identify new hereditary genes for early-onset gastric cancer patients (EOGC;<50 years old).
Methods: After germline exome sequencing in 20 EOGC patients and replication of relevant fndings by gene-panel sequencing in an independent cohort of 152 patients, CTNND1 stood out as an interesting candidate gene, since its protein product (p120ctn) directly interacts with E-cadherin. We proceeded with functional characterization by generating two knockout CTNND1 cellular models by gene editing and introducing the detected genetic variants using a lentiviral delivery system. We assessed β-catenin and E-cadherin levels, cell detachment, as well as E-cadherin localization and cell-to-cell interaction by spheroid modeling.
Results: Three CTNND1 germline variants [c.28_29delinsCT, p.(Ala10Leu); c.1105C>T, p.(Pro369Ser); c.1537A > G, p.(Asn513Asp)] were identifed in our EOGC cohorts. Cells encoding CTNND1 variants displayed altered E-cadherin levels and intercellular interactions. In addition, the p.(Pro369Ser) variant, located in a key region in the E-cadherin/p120ctn binding domain, showed E-cadherin mislocalization.
Conclusions: Defects in CTNND1 could be involved in germline predisposition to gastric cancer by altering E-cadherin and, consequently, cell-to-cell interactions. In the present study, CTNND1 germline variants explained 2% (3/172) of the cases, although further studies in larger external cohorts are needed.




The human gastric juice: a promising source for gastric cancer biomarkers

Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
  • Felípez, Nayra
  • Montori, Sheyla
  • Mendizuri, Naroa
  • Llach, Joan
  • Delgado, Pedro G.
  • Moreira, Leticia
  • Santamaría, Enrique
  • Albéniz Arbizu, Eduardo
  • Fernández Irigoyen, Joaquín
Gastric cancer (GC) is a major public health problem worldwide, with high mortality rates due to late diagnosis and limited treatment options. Biomarker research is essential to improve the early detection of GC. Technological advances and research methodologies have improved diagnostic tools, identifying several potential biomarkers for GC, including microRNA, DNA methylation markers, and protein-based biomarkers. Although most studies have focused on identifying biomarkers in biofluids, the low specificity of these markers has limited their use in clinical practice. This is because many cancers share similar alterations and biomarkers, so obtaining them from the site of disease origin could yield more specific results. As a result, recent research efforts have shifted towards exploring gastric juice (GJ) as an alternative source for biomarker identification. Since GJ is a waste product during a gastroscopic examination, it could provide a “liquid biopsy” enriched with disease-specific biomarkers generated directly at the damaged site. Furthermore, as it contains secretions from the stomach lining, it could reflect changes associated with the developmental stage of GC. This narrative review describes some potential biomarkers for gastric cancer screening identified in gastric juice., This was supported by grants from Instituto de Salud Carlos III (PI21/00333 and PI21/01181). Nayra Felípez has a grant from Departamento de Universidad, Innovación y Transformación Digital. Gobierno de Navarra (Ref 0011-1408-2022-000010).