Preliminary Study of BRF2 Expression in Subset of Head and Neck Cancers

Noor Akmar Nam^1,*, Siti Nur’ Aqilah Halimi², Muhammad Iqbal Mustaqim Abd Razak², Muhd Shamsuzzaman Ilham Fitri³, Tuan Norhayati Tuan Mahmood³, Asfizahrasby Mohd Rasoul⁴ 

Abstract

Introduction: Head and neck cancers (HNC) are abnormal cell proliferation in the mucosal surfaces involving several anatomical sites such as oral cavity, sinonasal cavity, pharynx, and larynx. In Malaysia, HNC especially involving the nasopharyngeal cancer is the fourth most common cancer, with total new cases of 2,222 detected in 2020. Determination of the potential biomarkers for early diagnosis of this disease is crucial. Transcription factor II B (TFIIB)-related factor 2 (BRF2) is one of the important transcription factors, regulating the RNA Polymerase III (Pol III) gene transcription. Dysregulation of Pol III transcription mediated by BRF2 lead to abnormal cell growth and cancer progression.  This study aimed to compile and analyse data on BRF2 expression related to HNC using online database and immunohistochemistry (IHC) analysis. Methods: Information regarding BRF2 protein and specific mRNA transcripts were retrieved from Human Protein Atlas (HPA), Oncomine, GEPIA, and cBioPortal databases. IHC analysis was performed on tissue microarrays (TMA) containing normal and a subset of HNC involving the lip tissues using BRF2 and PCNA antibodies as comparison. Results: HPA revealed overexpression of BRF2 protein in the nuclear region, detected in 25-75% cancer cells of all HNC cases (n=499) with staining intensity ranging from moderate to strong. In Oncomine, BRF2 shown differential expression between normal vs tumour tissues whereby 4/8 datasets showed upregulation of BRF2 transcripts. GEPIA also reported mRNA overexpression for BRF2 (8.6 vs 5.32) in head and neck squamous cell cancer (HNSC) compared to normal tissue. IHC staining revealed varying degree of BRF2 expression in HNC involving the lip as compared to normal tissue controls. Conclusion: Compiled data suggest that BRF2 is commonly overexpressed in HNC studied. Further study is essential to evaluate BRF2 expression in more HNC subsets as tissue distribution is heterogenous and involved large anatomical sites

Keywords: RNA Polymerase III, BRF2, Head and Neck Cancers, Oral Cancers, Biomarkers

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