Portal de investigación
Low miR200c expression in tumor budding of invasive front predicts worse survival in patients with localized colon cancer and is related to PD-L1 overexpression
Fecha de publicación:
Fecha Ahead of Print:
Autores de INCLIVA
Participantes ajenos a INCLIVA
- Gonzalez, J
- Santonja, F
Grupos y Plataformas de I+D+i
Abstract
At the histological level, tumor budding in colon cancer is the result of cells undergoing at least partial epithelial-to-mesenchymal transition. The microRNA 200 family is an important epigenetic driver of this process, mainly by downregulating zinc-finger E-box binding homeobox (ZEB) and transforming growth factor beta (TGF-beta) expression. We retrospectively explored the expression of the miR200 family, and ZEB1 and ZEB2, and their relationship with immune resistance mediated through PD-L1 overexpression. For this purpose, we analyzed a series of 125 colon cancer cases and took samples from two different tumor sites: the area of tumor budding at the invasive front and from the tumor center. We found significant ZEB overexpression and a reduction in miR200 in budding areas, a profile compatible with epithelial-to-mesenchymal transition. In multivariate analysis of the cases with localized disease, low miR200c expression in budding areas, but not at the tumor center, was an adverse tumor-specific survival factor (hazard ratio: 0.12; 95% confidence interval: 0.03-0.81; p = 0.02) independent of the clinical stage of the disease. PD-L1 was significantly overexpressed in the budding areas and its levels correlated with a mesenchymal transition profile. These results highlight the importance of including budding areas among the samples used for biomarker evaluation and provides relevant data on the influence of mesenchymal transition in the immune resistance mediated by PD-L1 overexpression.
© United States & Canadian Academy of Pathology 2018
Datos de la publicación
- ISSN/ISSNe:
- 0893-3952, 1530-0285
- Tipo:
- Article
- Páginas:
- 306-313
- PubMed:
- 30206410
MODERN PATHOLOGY NATURE PUBLISHING GROUP
Citas Recibidas en Web of Science: 31
Documentos
Filiaciones
Financiación
Proyectos y Estudios Clínicos
CONTRATOS MIGUEL SERVET TIPO II
Investigador Principal: GLORIA RIBAS DESPUIG
CPII14/00013 . INSTITUTO SALUD CARLOS III . 2015
Análisis de desregulación de microRNAs en lineas de cáncer de mama y estudios comparativo del cáncer de mama en mujeres jóvenes y mujeres mayores.
Investigador Principal: SARA OLTRA SANCHIS
2014/202 . MINISTERIO EDUCACION, CULTURA Y DEPORTE
CONTRATOS RIO HORTEGA
Investigador Principal: NOELIA TARAZONA LLAVERO
CM15/00246 . INSTITUTO SALUD CARLOS III
Enfermedad mínima residual en cánceres colorrectales de alto riesgo resecados. Valor de las biopsias líquidas en el seguimiento y análisis de la heterogeneidad tumoral.
Investigador Principal: ANDRÉS CERVANTES RUIPEREZ
PI15/02180 . INSTITUTO SALUD CARLOS III . 2016
CONTRATOS JUAN RODES
Investigador Principal: DESAMPARADOS RODA PEREZ
2016/197 . INSTITUTO SALUD CARLOS III . 2017
Cita
Martinez C,Oltra S,Rosello S,Roda D,Mongort C,Carrasco F,Gonzalez J,Santonja F,Tarazona N,Huerta M,Espi A,Ribas G,Ferrandez A,Navarro S,Cervantes A. Low miR200c expression in tumor budding of invasive front predicts worse survival in patients with localized colon cancer and is related to PD-L1 overexpression. Mod Pathol. 2019. 32. (2):p. 306-313. IF:5,988. (1).
Low miR200c expression in tumor budding of invasive front predicts worse survival in patients with localized colon cancer and is related to PD-L1 overexpression. Martinez C, Oltra S, Rosello S, Roda D, Mongort C, Carrasco F, Gonzalez J et al. MODERN PATHOLOGY. 2019 febrero 01. 32 (2):306-313. DOI:10.1038/s41379-018-0124-5. PMID:30206410.
