RT Journal Article
T1 NCAPH drives breast cancer progression and identifies a gene signature that predicts luminal a tumour recurrence
A1 Mendiburu-Eliçabe Garganta, Marina
A1 García Sancha, Natalia
A1 Corchado Cobos, Roberto
A1 Martínez López, Angélica
A1 Chang, Hang
A1 Mao, Jian Hua
A1 Blanco Gómez, Adrián
A1 García Casas, Ana
A1 Castellanos Martín, Andrés
A1 Salvador, Nélida
A1 Jiménez Navas, Alejandro
A1 Pérez Baena, Manuel Jesús
A1 Sánchez Martín, Manuel Adolfo
A1 Abad‐Hernández, María Del Mar
A1 Del Carmen, Sofía
A1 Claros Ampuero, Juncal
A1 Cruz Hernández, Juan Jesús
A1 Rodríguez Sánchez, César Augusto
A1 García Cenador, María Begoña
A1 García Criado, Francisco Javier
A1 Santamaría Vicente, Rodrigo
A1 Castillo Lluva, Sonia
A1 Pérez Losada, Jesús
AB Background: Luminal A tumours generally have a favourable prognosis but possess the highest 10‐year recurrence risk among breast cancers. Additionally, a quarter of the recurrence cases occur within 5 years post‐diagnosis. Identifying such patients is crucial as long‐term relapsers could benefit from extended hormone therapy, while early relapsers might require more aggressive treatment.Methods: We conducted a study to explore non‐structural chromosome maintenance condensin I complex subunit H’s (NCAPH) role in luminal A breast cancer pathogenesis, both in vitro and in vivo, aiming to identify an intratumoural gene expression signature, with a focus on elevated NCAPH levels, as a potential marker for unfavourable progression. Our analysis included transgenic mouse models overexpressing NCAPH and a genetically diverse mouse cohort generated by backcrossing. A least absolute shrinkage and selection operator (LASSO) multivariate regression analysis was performed on transcripts associated with elevated intratumoural NCAPH levels.Results: We found that NCAPH contributes to adverse luminal A breast cancer progression. The intratumoural gene expression signature associated with elevated NCAPH levels emerged as a potential risk identifier. Transgenic mice overexpressing NCAPH developed breast tumours with extended latency, and in Mouse Mammary Tumor Virus (MMTV)‐NCAPH ErbB2 double‐transgenic mice, luminal tumours showed increased aggressiveness. High intratumoural Ncaph levels correlated with worse breast cancer outcome and subpar chemotherapy response. A 10‐gene risk score, termed Gene Signature for Luminal A 10 (GSLA10), was derived from the LASSO analysis, correlating with adverse luminal A breast cancer progression.Conclusions: The GSLA10 signature outperformed the Oncotype DX signature in discerning tumours with unfavourable outcomes, previously categorised as luminal A by Prediction Analysis of Microarray 50 (PAM50) across three independent human cohorts. This new signature holds promise for identifying luminal A tumour patients with adverse prognosis, aiding in the development of personalised treatment strategies to significantly improve patient outcomes.
PB Wiley
SN 2001-1326
YR 2024
FD 2024
LK https://hdl.handle.net/20.500.14352/101501
UL https://hdl.handle.net/20.500.14352/101501
LA eng
NO Mendiburu‐Eliçabe, Marina, Natalia García‐Sancha, Roberto Corchado‐Cobos, Angélica Martínez‐López, Hang Chang, Jian Hua Mao, Adrián Blanco‐Gómez, et al. «NCAPH Drives Breast Cancer Progression and Identifies a Gene Signature That Predicts Luminal a Tumour Recurrence». Clinical and Translational Medicine 14, n.o 2 (febrero de 2024): e1554. https://doi.org/10.1002/ctm2.1554.
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Comisión Europea
NO Junta de Castilla y León
DS Docta Complutense
RD 12 abr 2025