Journal of Kerman University of Medical Sciences

Cathepsin B and Caveolin-1 as Molecular Indicators of Tumor-Free Margins in Oral Squamous Cell Carcinoma

Articles in Press

Document Type : Original Article

Authors

Zahra Delavarian 1
Atessa Pakfetrat 1
Nooshin Mohtasham 2
Farnaz Mohajertehran 2
Hanieh Paik 3
Negin Samiee 4

1 Oral and Maxillofacial Disease Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Dental Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Research Committee, Faculty of Dentistry, Kurdistan University of Medical Sciences, Sanandaj, Iran

4 Oral and Maxillofacial Medicine Department, Faculty of Dentistry, Kurdistan University of Medical Sciences, Sanandaj, Iran

Abstract
Introduction: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and is frequently associated with poor prognosis and high recurrence rates. Despite histologically tumor‑free margins, subclinical molecular alterations may persist in adjacent tissues and contribute to local recurrence and the phenomenon of field cancerization. Identification of reliable molecular biomarkers may improve the detection of biologically altered margins beyond conventional histopathological evaluation. This study evaluated the expression of Cathepsin B (Cat‑B) and Caveolin‑1 (Cav‑1) as potential molecular indicators of tumor progression and surgical margin status in OSCC.
Methods: In this cross‑sectional case–control molecular study, messenger RNA (mRNA) expression of Cat‑B and Cav‑1 was quantified using quantitative real‑time polymerase chain reaction (qRT‑PCR) in 117 formalin‑fixed paraffin‑embedded (FFPE) samples, including 28 OSCC tumors, 28 paired tumor‑free surgical margins, 33 oral lichen planus (OLP) lesions, and 28 healthy controls. Statistical analyses were performed using the Kruskal–Wallis test, Mann–Whitney U test, and Spearman’s correlation analysis.
Results: Both Cat‑B and Cav‑1 were significantly overexpressed in OSCC tissues compared with tumor‑free margins and healthy controls (p < 0.001). Their expression correlated positively with tumor grade (Cat‑B: p = 0.01; Cav‑1: p = 0.003) and clinical stage (Cat‑B: p = 0.02; Cav‑1: p = 0.01). Only one margin sample (3.4%) showed detectable expression, suggesting limited molecular extension beyond histologically normal tissue.
Conclusion: The concurrent upregulation of Cat‑B and Cav‑1 supports their potential role as complementary molecular biomarkers associated with tumor progression and margin involvement. These findings align with the concept of field cancerization and may assist molecular margin assessment and risk stratification in OSCC. Further validation through protein‑level analyses and larger multicenter studies with clinical follow‑up is warranted.

Keywords

Carcinoma Squamous Cell
Cathepsin B
Caveolin 1
Margins of Excision
Biomarkers
Real-Time Polymerase Chain Reaction
Subjects
Journal of Kerman University of Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 31 October 2026

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