NCAPH drives breast cancer progression and identifies a gene signature that predicts luminal a tumour recurrence

作者：Marina Mendiburu‐Eliçabe, Natalia García‐Sancha, Roberto Corchado‐Cobos, Angélica Martínez‐López, Hang Chang, Jian‐Hua Mao, Adrián Blanco‐Gómez, Ana García‐Casas, Andrés Castellanos‐Martín, Nélida Salvador, Alejandro Jiménez‐Navas, Manuel Jesús Pérez‐Baena, Manuel Sánchez‐Martín, María del Mar Abad‐Hernández, Sofía del Carmen, Juncal Claros‐Ampuero, Juan Jesús Cruz, César Augusto Rodríguez‐Sánchez, María Begoña García Cenador, Francisco Javier García‐Criado, Rodrigo Santamaría, Sonia Castillo‐Lluva, Jesús Pérez‐Losada · 发表于：Clinical and Translational Medicine · 年份：2024 · DOI：10.1002/ctm2.1554 · 被引用次数：7 · 研究领域：Breast Cancer Treatment Studies、Genomics and Chromatin Dynamics、BRCA gene mutations in cancer

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: 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 ...