SRS133 - Nucleolin (NCL) in clinical breast cancer, the prognostic and therapeutic implications

Abstract Introduction ucleolin (NCL) is a multifunctional nuclear protein that interacts with chromatin and regulates ribosome biogenesis, cell growth, and transcription. Aberrant NCL expression has been reported in several solid cancers, and NCL can also localise to the cell surface, where it acts as a receptor for proteins, lectins, and viruses. These findings raise interest in NCL as a potential therapeutic target. We investigated the expression of NCL in breast cancer and explored its clinical and therapeutic implications. Methods NCL expression was examined in breast cancer tissues and correlated with tumour stage, molecular subtype, receptor status, and survival outcomes. Validation and extended analyses were performed using TCGA datasets. Results Breast cancer tissues showed significantly higher NCL expression compared with normal mammary tissues (P = 0.025). Patients with high NCL had significantly shorter overall survival (P = 0.013) and reduced disease-free survival (P = 0.009). Stronger associations were observed in tumours with high aromatase (P = 0.011), low EGFR (P = 0.004), and high ERBB4 (P = 0.007). TCGA data further demonstrated that NCL expression was strongly correlated with patient responses to neoadjuvant chemotherapy (P = 7.2 × 10−7) and adjuvant chemotherapy (P = 0.021), particularly in TNBC and Luminal-A subtypes, but not in HER2(+)/ER(−) cancers. Conclusions NCL is aberrantly expressed in breast cancer and is associated with poor clinical outcomes. Subgroups with distinct molecular features show stronger associations, highlighting opportunities for NCL-targeted therapeutic approaches.