Sara Abdeljalil

Egypt

Serum Exosomal LncRNA NAMPT-AS in Breast Cancer: From Molecular Function to Clinical Implications

Sara M. Abdeljalil a, Sherehan G. Abdelhamid b, Ramy Ghali c, Montaser B. Yasser d, Mohamed M. Kamal b, e, f, * and Dina H. Kassem b,*

a The Environmental Monitoring Center, Central Administration of Environmental Affairs, Ministry of Health and Population, Cairo, Egypt
b Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Ain Shams University, 11566, Cairo, Egypt
c Department of Clinical Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
d Bioinformatics Program, Center for Informatics Sciences (CIS), School of Information Technology and Computer Science (ITCS), Nile University, Giza, Egypt
e Pharmacology and Biochemistry Department, Faculty of Pharmacy, The British University in Egypt
Cairo, Egypt
f Health Research Centre of Excellence, Drug Research and Development Group, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt

Abstract

Background

Breast cancer (BC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Exosomes are small extracellular vesicles that mediate intercellular communication by transporting functional cargos such as proteins and non-coding RNAs. NAMPT-AS has recently emerged as a potent oncogenic long non-coding RNA across several cancer types; however, its circulating exosomal profile in breast cancer (BC) remains largely uncharacterized. This study provides a comprehensive evaluation of serum exosomal NAMPT-AS in BC patients and investigates its potential contribution to disease initiation and clinical progression.

Methods

Serum exosomes were obtained from patients with BC (n=40) and healthy controls (n=28). Relative expression levels of NAMPTAS and NAMPT mRNA in serumderived exosomes were quantified using quantitative reverse transcription PCR (qRTPCR). Exosomal characterization was carried out by transmission electron microscopy, nanoparticle tracking analysis, and western blotting for established exosomal markers. Correlation analyses were performed to determine the association between exosomal NAMPTAS and exosomal NAMPT. Their association with clinicopathological characteristics was examined and their diagnostic and prognostic performance were further assessed using receiver operating characteristic (ROC) curve analyses.

Results

Serum exosomal NAMPT-AS showed a significant upregulation in BC patients compared to healthy controls. High expression was associated with positive lymph node involvement (p= 0.035) and a trend towards distant metastasis (p=0.072). Moreover, its levels demonstrated positive correlations with exosomal NAMPT mRNA (r=0.298, p=0.014). Higher NAMPT-AS expression enhanced the discriminatory ability of serum NAMPT in early disease stages with area under the curve (AUC) of 0.716 (p=0.006), supporting their combined potential as a non-invasive biomarker panel.

Conclusions

The current study demonstrates that the aberrant expression of lncRNA NAMPT-AS is strongly associated with BC initiation and disease progression. This underscores its significant clinical implications as a novel non-invasive diagnostic and prognostic biomarker in BC. Further investigations into the molecular mechanisms underlying NAMPT-AS mediated oncogenic effects and validating these findings in larger patient cohorts may pave the way for the development of NAMPT-AS targeted therapeutic approaches to improve breast cancer management and patient outcomes.