Molecular Interplays Between Cell Invasion and Radioresistance That Lead to Poor Prognosis in Head-Neck Cancer

Background Cancer metastasis and recurrence after radiotherapy are the significant causes of poor prognosis in head-neck cancer (HNC). Clinically, it is commonly found that patients with either condition may accompany the outcome of the other. We hypothesized that HNC cells might exhibit a cross-phenotypic attribute between cell invasion and radioresistance. To discover effective biomarkers for the intervention of aggressive cancer at one time, the potential molecules that interplay between these two phenotypes were investigated. Materials and Methods Three isogenic HNC cell sublines with high invasion or radioresistance properties were established. Transcriptomic and bioinformatic methods were used to globally assess the phenotypic-specific genes, functional pathways, and co-regulatory hub molecules. The associations of gene expressions with patient survival were analyzed by Kaplan-Meier plotter, a web-based tool, using the HNSCC dataset (n=500). The molecular and cellular techniques, including RT-qPCR, flow cytometry, cell invasion assay, and clonogenic survival assay, were applied. Results The phenotypic crosstalk between cell invasion and radioresistance was validated, as shown by the existence of mutual properties in each HNC subline. A total of 695 genes was identified in associations with these two phenotypes, including 349 upregulated and 346 downregulated in HNC cells. The focal adhesion mechanism showed the most significant pathway to co-regulate these functions. In the analysis of 20 up-regulatory genes, a general portrait of correlative expression was found between these phenotypic cells (r=0.513, p=0.021), and nine molecules exhibited significant associations with poor prognosis in HNC patients (HR>1, p