Intriguingly, positive correlation was observed among HPRT1 expression, AMPK pT172, and RRM1 pT52 in these recurrent GBM samples (Fig. 8g–i), suggesting that TMZ strongly activated HPRT1/AMPK/RRM1 signal cascade in human GBM specimens and that this cascade may contribute to recurrence and refractory to TMZ of brain tumors. This evidence concerns the gene PRKAA2 and glioblastoma.