Differential gene expression analysis reveals signaling pathways of proliferation, angiogenesis and metastasis is associated with interferon suppression in advanced hypopharyngeal cancer cells

Hypopharyngeal cancer (HPC) is a highly aggressive cancer with a poor prognosis due to frequent metastasis and resistance to therapy. However, genes associated with the malignancy of advanced HPC remain to be elucidated. To investigate molecular changes associated with HPC progression, RNA sequencing was performed to compare transcriptomic profiles between parental FaDu HPC cells and advanced FaDu cells (FaDuex) derived from late-stage xenograft tumors. The present analysis revealed 86 markedly upregulated genes and 166 markedly downregulated genes in FaDuex cells compared with FaDu cells. Gene set enrichment analysis revealed enrichment of pathways associated with epithelial-mesenchymal transition and cell proliferation among upregulated genes, whereas downregulated genes were associated with metastasis inhibition, angiogenesis suppression and immune response regulation. Notably, several interferon (IFN)-stimulated genes were suppressed in advanced cells, indicating impaired IFN signaling and reduced antitumor immune responses. The most notable changes in the expression levels of genes associated with these tumor characteristics were then validated using quantitative PCR. These findings suggest that genes associated with tumor malignancy and immunosuppressive pathways potentially contribute to HPC progression and highlight potential molecular targets for diagnostic and therapeutic intervention in the future.