The Clinicopathological Significance and Bioinformatic Characterization of TFRC1 in Oral Squamous Cell Carcinoma
TFRC1 in Oral Squamous Cell Carcinoma
Keywords:
Immunohistochemistry, Neoplasm Grading, Squamous Cell Carcinoma of Head and Neck, Tumor Biomarkers, Transferrin ReceptorAbstract
Background: Oral squamous cell carcinoma (OSCC) shows marked biological variability between patients. Transferrin receptor 1 (TFRC1) regulates cellular iron acquisition and may support tumour growth; however, its significance in OSCC has not been clearly defined. This study examined TFRC1 protein expression in OSCC tissue in relation to clinicopathological features and used TCGA-HNSC data to assess its transcript levels and, on an exploratory basis, its association with survival.
Methods: This retrospective cross-sectional and bioinformatic study of OSCC biopsies, with TCGA-HNSC validation, was conducted at Ziauddin University, Karachi (June 2025–June 2026). Immunohistochemistry (IHC) for TFRC1 was performed on 146 OSCC biopsies, and staining status was compared across clinicopathological parameters. TCGA-HNSC transcript expression and prognostic significance were evaluated using UALCAN and Kaplan–Meier analysis, respectively.
Results: TFRC1 expression was positive in 110/146 (75.3%) OSCC cases and significantly associated with histological differentiation (Chi-square test, p = 0.04), but not with gender (p = 0.07), anatomical site (p = 0.41), or age (p = 0.91). TCGAHNSC analysis showed significantly higher TFRC1 transcript expression in primary tumours than normal tissues (p < 1 × 10⁻¹²), with an increasing trend across tumour grades, although not all pairwise comparisons were significant. Kaplan–Meier analysis showed no significant association with overall survival in the overall cohort (p = 0.47) or grade-stratified analysis (p = 0.15).
Conclusion: TFRC1 was frequently expressed in OSCC and significantly associated with histological differentiation. In TCGA-HNSC, TFRC1 mRNA levels were higher in tumour than in normal tissue. Taken together, these results indicate dysregulated iron homeostasis in OSCC and support further evaluation of TFRC1 as a candidate biomarker.
DOI: https://doi.org/10.59564/amrj/04.04/008
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Copyright (c) 2026 Dr Alizae Hemani, Dr Faraz Ahmed Baig, Dr Syeda Zehra Ahmed, Dr Ummiya Tahir

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