%0 Journal Article
%A Mendiburu-Eliçabe Garganta, Marina
%A García Sancha, Natalia
%A Corchado Cobos, Roberto
%A Martínez López, Angélica
%A Chang, Hang
%A Mao, Jian Hua
%A Blanco Gómez, Adrián
%A García Casas, Ana
%A Castellanos Martín, Andrés
%A Salvador, Nélida
%A Jiménez Navas, Alejandro
%A Pérez Baena, Manuel Jesús
%A Sánchez Martín, Manuel Adolfo
%A Abad‐Hernández, María Del Mar
%A Del Carmen, Sofía
%A Claros Ampuero, Juncal
%A Cruz Hernández, Juan Jesús
%A Rodríguez Sánchez, César Augusto
%A García Cenador, María Begoña
%A García Criado, Francisco Javier
%A Santamaría Vicente, Rodrigo
%A Castillo Lluva, Sonia
%A Pérez Losada, Jesús
%T NCAPH drives breast cancer progression and identifies a gene signature that predicts luminal a tumour recurrence
%D 2024
%@ 2001-1326
%U https://hdl.handle.net/20.500.14352/101501
%X 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.
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