In contrast, NOTCH3-positive cases were not necessarily NRF2-positive (Fig. 2c), which suggested the presence of alternative regulators for NOTCH3. Notably, double-positive patients showed significantly poorer prognoses than the remaining cases (Fig. 2d, e and Supplementary Fig. 3b), suggesting that the combination of NRF2 and NOTCH3 makes cancers malignant and that NOTCH3 contributes to cancer malignancy when it is co-expressed with NRF2 target genes in NRF2-activated NSCLCs. This evidence concerns the gene NOTCH3 and cancer.