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

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genetics

Background:

• Nucleolin (NCL) is a multifunctional protein implicated in cancer development.
• Anti-NCL therapies demonstrate potent cytotoxic effects, particularly in triple-negative breast cancer (TNBC) models.
• Clinical utility of NCL in stratifying cancer patients remains underexplored.

Purpose of the Study:

• To investigate the prognostic value of NCL expression in breast cancer.
• To determine if NCL expression can stratify breast cancer patients across different subtypes.
• To explore the association of NCL with clinical characteristics in breast cancer.

Main Methods:

• Utilized two independent patient cohorts (n=216 and n=661) for analysis.
• Employed univariate and multivariate Cox-regression analyses to assess prognostic value.
• Conducted transcriptomic analyses using The Cancer Genome Atlas (TCGA) database.

Main Results:

• NCL mRNA expression levels serve as independent markers of poor survival, irrespective of tumor size and lymph node status (n=216).
• A significant association between NCL expression and poor survival was observed in TNBC patients (n=40).
• Transcriptomic data revealed distinct gene expression profiles in tumors with low versus high NCL mRNA levels, suggesting biological heterogeneity.

Conclusions:

• NCL is an independent prognostic marker in breast cancer.
• NCL expression levels can differentiate tumor subtypes with distinct molecular profiles.
• Targeting NCL represents a promising therapeutic strategy, especially for tumors with high NCL expression, to enhance breast cancer management.