Nucleolin expression has prognostic value in neuroblastoma patients

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Neuroblastoma (NB) is the most common extra-cranial solid tumor in infants, accounting for 15% of childhood cancer deaths.
• The prognostic value of Nucleolin (NCL) in NB was investigated to identify new biomarkers.

Purpose of the Study:

• To evaluate the prognostic significance of Nucleolin (NCL) expression in neuroblastoma (NB).
• To determine if NCL expression can serve as an independent prognostic marker in NB patients.

Main Methods:

• Retrospective analysis of NCL protein expression in NB tumor samples before and after chemotherapy.
• Assessment of NCL mRNA expression in two independent cohorts: qPCR20 (n=20, stage 4 NB) and MultiPlatform786 (n=786, all stages).
• Kaplan-Meier survival analysis and log-rank tests were used to evaluate overall survival (OS) and event-free survival (EFS).

Main Results:

• NCL protein was overexpressed in NB tumors and higher in stage 4 compared to earlier stages; it was down-modulated post-chemotherapy.
• High NCL mRNA expression was significantly associated with lower OS and EFS in stage 4 NB patients (qPCR20 cohort).
• Multivariate analysis in the MultiPlatform786 cohort confirmed NCL's independent prognostic value, stratifying survival in high-risk subgroups (e.g., >18 months, stage 4, MYCN non-amplified).
• Significant correlations were found between NCL expression and MYCN, MYC, and TERT, with enrichment of MYC target genes and telomerase maintenance pathways.

Conclusions:

• Nucleolin (NCL) is a novel and independent prognostic marker for neuroblastoma (NB).
• NCL expression provides valuable prognostic information, even when adjusted for established markers like age, INSS stage, and MYCN status.
• NCL may play a role in NB pathogenesis and could be a target for future therapeutic strategies.