Introduction: Oral squamous cell carcinoma is a biologically aggressive malignancy in which molecular alterations may extend beyond visible tumor tissue into surgical margins. Long non-coding RNAs, particularly LNC-NORAD, may influence genomic stability, stress responses, and tumor progression. This study aimed to assess LNC-NORAD expression changes in tumor and surgical margin samples of OSCC.

Material and methods: This descriptive cross-sectional study was conducted at Tabriz University of Medical Sciences in 2024. Using convenience sampling, 100 specimens comprising 50 oral squamous cell carcinoma tissues and 50 matched healthy surgical margins were collected from 50 patients. LNC-NORAD expression was quantified by real-time PCR and evaluated alongside age, sex, smoking status, tumor site and size, histological grade, invasion characteristics, TNM stage, lymph node involvement, and margin status.

Results: LNC-NORAD expression was significantly higher in OSCC tumor tissues than in matched healthy surgical margins (3.18 ± 1.07 vs. 1.24 ± 0.43; P<0.001). Increased tumoral expression was associated with smoking, larger tumor size, poorer histological differentiation, deeper invasion, perineural invasion, advanced TNM stage, and lymph node metastasis. By contrast, no significant associations were observed with sex, anatomical tumor site, or lymphovascular invasion.

Conclusion: LNC-NORAD is markedly upregulated in OSCC tissues compared with matched surgical margins and is closely associated with several indicators of tumor aggressiveness. These findings suggest that this long non-coding RNA may serve as a useful molecular marker for identifying biologically advanced and clinically high-risk oral squamous cell carcinoma.