Remarkably, low transcript levels of seven from 11 ‘hub proteins’ (ALDH7A1, CAD, CANT1, GOT1, MTHFD1, PYGB, and SARS) were associated with a more aggressive clinical outcome, that is, poor patient prognosis, using data from patients with HNSCC from the public databases TCGA, GSE41613, E-MTAB-1328, and GSE65858. Here, MTHFD1 is linked to head and neck squamous cell carcinoma.