Tehran University of Medical Sciences Journal of Craniomaxillofacial Research 2345-5489 12 2 2025 09 23 100 105 EN Pegah Babaei Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran. Amir Jalal Abbasi Department of Oral and Maxillofacial Surgery, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran; Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran. Abdolreza Mohamadnia Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran, And Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Mahta Malek Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran. Masoume Farhangiyan Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran. Naghmeh Bahrami Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2025 08 05 2025 08 12 Introduction: Oral squamous cell carcinoma (OSCC) is a widespread, aggressive disease with low survival rates due to late diagnosis and a lack of effective, noninvasive biomarkers. The nuclear cap-binding protein subunit 2 (NCBP2), involved in mRNA regulation, has been implicated in tumorigenesis. This study aimed to evaluate NCBP2 mRNA expression in plasma samples from patients with OSCC to assess its potential as a circulating diagnostic biomarker.  Materials and Methods: Fifteen patients with histologically proven OSCC and fifteen age-matched healthy controls participated in a case-control study. Plasma was isolated from peripheral blood in an RNase-free environment. Total RNA was extracted and reverse-transcribed into cDNA. Gene-specific primers and SYBR Green chemistry were used in quantitative real-time PCR. Using GAPDH as the reference gene, relative expression was computed using the 2^–ΔΔCt technique. Independent t-tests were used to examine the data, with a significance level of p<0.05.  Results: There was a 1.89-fold increase in NCBP2 mRNA expression in the OSCC group when compared to controls (p<0.001). Ten out of fifteen OSCC patients had positive NCBP2 expression, compared to five out of fifteen healthy controls who had detectable levels. Age, sex, and smoking status did not show significant correlations with gene expression.  Conclusion: The observed overexpression of circulating NCBP2 mRNA in OSCC patients supports its potential as a non-invasive biomarker for early detection. Integration of NCBP2 testing into liquid biopsy protocols could enhance diagnostic accuracy and improve patient outcomes. Further studies with larger sample sizes and functional validation are recommended.  Keywords: Oral squamous cell carcinoma (OSCC); Nuclear cap-binding protein2 (NCBP2); liquid biopsy; RT-qPCR; Circulating mRNA; Non-invasive biomarker.  https://jcr.tums.ac.ir/index.php/jcr/article/view/555 https://jcr.tums.ac.ir/index.php/jcr/article/download/555/448