Fig. 6: The PI3K-phospho-YBX1 axis in basal and mesenchymal HNC subtypes predicts patient prognosis.

A YBX1 expression in patients’ HNC did not vary between basal (n = 31) and mesenchymal subtypes (n = 27) however, phospho-YBX1 was significantly higher in the basal group. Data are shown as mean ± SEM. The comparison between the two groups was performed using an unpaired two-tailed t test (* p-value = 0.0246). B The correlation of ssGSEA scores between the hallmark EMT gene set and YBX1 (R = 0.2187, two-sided p-value = 0.091) or phospho-YBX1 (R = –0.3438, p-value < 0.01) from basal and mesenchymal HNC (n = 58, Spearman’s correlation). 95% confidence bands of the best-fit line are shown in pink. C Heatmap showing unsupervised clustering of HNC samples correlating levels of YBX1 and EMT ssGSEA with the basal subtype, and levels of phospho-YBX1 and PI3K/AKT/mTOR signalling ssGSEA with the mesenchymal subtype. D HR and adjusted Kaplan-Meier curve analyses of pYBX1 for overall survival of n = 337 patients from the TCGA-HNC cohort. HRs were estimated using multivariate Cox proportional hazard models. Asterisks indicate statistical significance per clinically-relevant factor. HR estimates are shown as dots at the centre of error bars and error bars represent 95% confidence intervals of hazard ratios by two-sided Wald test. E Neoplasm histologic grade, neoplasm disease stage, and lymph node stage from the TCGA-HNC were compared for p-YBX1^Hi and p-YBX1^Lo HNC. p-value was calculated using Pearson’s Chi-square test (*p-value = 0.0255, *** p-value = 0.0006, ****p-value < 0.0001). F YBX1 and phospho-YBX1 levels in the p-YBX1^Lo (n = 71) and p-YBX1^Hi (n = 274) patient groups. Data are shown as mean ± SEM. The comparison between the two groups was performed using an unpaired two-tailed t test (****p-value < 0.0001). G Volcano plot of differentially expressed proteins between p-YBX1^Lo (n = 71) and p-YBX1^Hi (n = 241) using the TCGA-HNC RPPA data. Labelled proteins associated with the PI3K/mTOR signalling were upregulated in p-YBX1^Hi tumours. Significant differentially expressed proteins with two-sided q-value < 0.05 are highlighted in pink, NS (not significant). H IHC staining for phospho-YBX1 and PDPN in patient HNC tissue arrays. Expression of p-YBX1 and PDPN was mutually exclusive in proliferative cells at the core of primary tumours and the invasive front. Source data are provided as a Source Data file.