High expression of novel biomarker TBRG4 promotes the progression and invasion of oral squamous cell carcinoma

Background: Transforming growth factor beta regulator 4 (TBRG4) is a potential prognostic indicator in various cancers, especially squamous cell carcinomas, and is associated with disease amelioration and poor outcomes. The study aimed to assess the expression pattern of TBRG4 in patients with operable oral squamous cell carcinoma (OSCC) to understand its role in tumour progression using indicators of disease outcome like tumour stage, grade, nodal metastasis, and pattern of invasion. Methods: TBRG4 expression was assessed by analyzing 51 cancer and adjacent non-cancerous tissues of OSCC patients using quantitative real-time PCR, and Western blot. TBRG4 expression was also analysed in The Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset using the UALCAN tool (http://ualcan.path.uab.edu/). The relationship between TBRG4 expression and the patient's prognosis was analysed using Kaplan-Meier plotter. Results: Both mRNA and protein levels of TBRG4 were significantly increased in OSCC tissues. The TBGR4 expression was significantly associated with advanced stages (III and IV) and the worst pattern of invasion (WPOI-4 and 5). High TBRG4 expression was also significantly associated with reduced overall survival (p = 0.011). In addition, the analysis of TBRG4 gene expression and clinical data from TCGA, identified that TBRG4 was highly expressed in HPV negative OSCC patients and positively correlated with worst overall survival. Conclusion: The present study suggests that the high expression of TBRG4 might serve as a novel prognostic biomarker for HPV-negative OSCC, which can be validated by future additional investigations in larger cohorts along with functional studies.