Amplification and overexpression of a novel m6A reader FXR1 are associated with poor prognosis in head and neck squamous cell carcinoma

BACKGROUND: Fragile X-related protein 1 (FXR1), an RNA-binding protein (RBP) implicated in various cancers, has emerged as a potential contributor to the progression of head and neck squamous cell carcinoma (HNSCC). OBJECTIVES: The aim of the study was to comprehensively analyze FXR1 genetic alterations, mRNA expression, protein levels, and immune infiltration in HNSCC, in order to elucidate its molecular role and therapeutic potential. MATERIAL AND METHODS: Data from The Cancer Genome Atlas (TCGA)-HNSCC cohort was analyzed. Copy number variation (CNV) was assessed using cBioPortal, FXR1 expression profiling was performed using the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), and immunohistochemistry (IHC) examination was conducted using the Human Protein Atlas (HPA). The TIMER 2.0 and TISIDB databases were employed for immune infiltration analysis. RESULTS: Genetic alterations in FXR1, including DNA amplification, were observed in 22% of HNSCC patients and were significantly correlated with elevated mRNA expression. FXR1 mRNA and protein levels were upregulated in HNSCC tumors, and this upregulation was associated with poor prognosis. The expression of FXR1 was also correlated with clinical features, including disease stage, grade, metastasis, and human papillomavirus (HPV) status. Immune infiltration analysis revealed a negative correlation between FXR1 mRNA expression and CD8+ T cells, suggesting a potential role in immune modulation. CONCLUSIONS: FXR1 may serve as a potential biomarker and immune regulator in HNSCC, with genetic alterations influencing its mRNA expression. This study sheds light on the multifaceted role of FXR1 in the progression of HNSCC, and suggests potential avenues for targeted therapeutic strategies. Further research, including functional experiments and large-scale cohort analyses, is warranted to validate and translate these findings into clinical applications.