FOXM1 Expression in Invasive Ductal Breast Carcinoma of No Special Type: Insights from RNA-seq and Immunohistochemical Analysis

Ohara, M.; Mikami, E.; Inohana, W.; Kurosawa, T.; Nakame, A.; Sakakibara, A.; Ichinose, Y.; Fujimoto, A.; Nukui, A.; Asano, A.; Shimada, H.; Asai, K.; Hirasaki, M.; Yokogawa, H.; Matsuura, K.; Ishiguro, H.; Hasebe, T.; Fujiuchi, N.; Osaki, A.; Saeki, T.

doi:10.1101/2025.09.07.674683

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bioRxiv · 10.1101/2025.09.07.674683

FOXM1 Expression in Invasive Ductal Breast Carcinoma of No Special Type: Insights from RNA-seq and Immunohistochemical Analysis

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Abstract

BackgroundInvasive ductal carcinoma of no special type (IDC-NST) is the most common subtype of breast cancer, characterized by significant clinical heterogeneity. Forkhead box M1 (FOXM1) is a key transcription factor involved in cell cycle regulation and tumor progression, but its expression profile and clinical significance in IDC-NST remain incompletely understood. MethodsWe analyzed FOXM1 expression in a cohort of 100 IDC-NST patients using RNA sequencing and immunohistochemistry (IHC). FOXM1 mRNA levels were quantified, and protein expression was scored based on the percentage of positive tumor cells. Differentially expressed genes (DEGs) between high and low FOXM1 expression groups were identified, followed by pathway enrichment and protein-protein interaction (PPI) network analyses. The prognostic value of FOXM1 was evaluated by recurrence-free survival (RFS) analysis. ResultsFOXM1 protein expression correlated significantly with mRNA abundance in 22 representative cases (p < 0.05). Receiver operating characteristic (ROC) curve analysis identified a cut-off value of 4.954 CPM for FOXM1 mRNA to predict recurrence (AUC = 0.642). High FOXM1 expression was associated with larger tumor size, higher histological grade, and negative hormone receptor status. Patients with high FOXM1 expression exhibited significantly poorer 5-year RFS (73.6% vs. 92.3%, p < 0.001). Multivariate analysis confirmed FOXM1 as an independent prognostic factor (HR 15.26; p = 0.026). Transcriptomic profiling revealed 190 upregulated and 197 downregulated genes in the FOXM1-high group, enriched in cell cycle and mitotic pathways. PPI network analysis positioned FOXM1 as a central hub coordinating genes involved in chromosomal stability and mitosis. ConclusionsFOXM1 overexpression is a strong independent predictor of poor prognosis in IDC-NST and plays a critical role in tumor proliferation and genome integrity. These findings support FOXM1 as a potential prognostic biomarker and therapeutic target, warranting further investigation into FOXM1-targeted therapies for breast cancer management.

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Ohara, M., Mikami, E., Inohana, W., Kurosawa, T., Nakame, A., Sakakibara, A., Ichinose, Y., Fujimoto, A., Nukui, A., Asano, A., Shimada, H., Asai, K., Hirasaki, M., Yokogawa, H., Matsuura, K., Ishiguro, H., Hasebe, T., Fujiuchi, N., Osaki, A., Saeki, T.. 2025-09-12. FOXM1 Expression in Invasive Ductal Breast Carcinoma of No Special Type: Insights from RNA-seq and Immunohistochemical Analysis. https://doi.org/10.1101/2025.09.07.674683

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