Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes

Abstract

<i>Background:</i> Nucleolin (NCL) is a multifunctional protein with oncogenic properties. Anti-NCL drugs show strong cytotoxic effects, including in triple-negative breast cancer (TNBC) models, and are currently being evaluated in phase II clinical trials. However, few studies have investigated the clinical value of <i>NCL</i> and whether <i>NCL</i> stratified cancer patients. Here, we have investigated for the first time the association of <i>NCL</i> with clinical characteristics in breast cancers independently of the different subtypes. <i>Methods:</i> Using two independent series (<i>n</i> = 216; <i>n</i> = 661), we evaluated the prognostic value of <i>NCL</i> in non-metastatic breast cancers using univariate and/or multivariate Cox-regression analyses. <i>Results:</i> We reported that <i>NCL</i> mRNA expression levels are markers of poor survivals independently of tumour size and lymph node invasion status (<i>n</i> = 216). In addition, an association of <i>NCL</i> expression levels with poor survival was observed in TNBC (<i>n</i> = 40, overall survival (OS) <i>p</i> = 0.0287, disease-free survival (DFS) <i>p</i> = 0.0194). Transcriptomic analyses issued from The Cancer Genome Atlas (TCGA) database (<i>n</i> = 661) revealed that breast tumours expressing either low or high <i>NCL</i> mRNA expression levels exhibit different gene expression profiles. These data suggest that tumours expressing high <i>NCL</i> mRNA levels are different from those expressing low <i>NCL</i> mRNA levels. <i>Conclusions: NCL</i> is an independent marker of prognosis in breast cancers. We anticipated that anti-NCL is a promising therapeutic strategy that could rapidly be evaluated in high <i>NCL</i>-expressing tumours to improve breast cancer management.