Identification and validation of the role of c-Myc in head and neck squamous cell carcinoma

BACKGROUND: Many studies have shown that c-Myc plays a critical role in tumorigenesis. However, the molecular role of c-Myc in head and neck squamous cell carcinoma (HNSC) remains unclear. METHODS: Several biological databases, including UALCAN, TIMER2.0, TCGAportal, GEPIA, KM plotter, OncoLnc, LinkedOmics, GSCA, and TCIA, were used to analyze the molecular role of c-Myc in HNSC. The expression levels of c-Myc were validated by real-time PCR (RT–PCR) and Western blot in CAL-27 cells. RESULTS: The expression of c-Myc mRNA were significantly increased in HPV-negative HNSC tissues. The expression of c-Myc gene level was correlated with TP53 mutation status. HNSC also showed hypomethylated c-Myc compared with normal tissues. c-Myc was identified as an ominous prognostic factor for HNSC patients and correlated with immune infiltrating levels. Moreover, high c-Myc expression was associated with decreased expression of a series of immune checkpoints, resulting in a dampened immune response. c-Myc potentially mediated IL-17 signaling pathway and Th1 and Th2 cell differentiation. Inhibition of c-Myc expression increased apoptosis of CAL-27 cells. CONCLUSIONS: These findings suggest a new mechanism of c-Myc in the prognosis of HNSC, implying the potential of c-Myc as a therapeutic target for HNSC patients.