PTC tumors are significantly and positively enriched for gene sets corresponding NRF2 related functions. (A) A gene set (V$NRF2_Q4) consisting of NFE2L2 transcriptional targets was significantly and positively enriched in PTC tumor relative to non-malignant tissues. For PTC tumors, normalized enrichment score (ES) = 1.42, p-value = 0.023. ES (green line) represent the probability that the gene set is positively (left side) or negatively (right side) enriched in a ranked gene list. Genes are first ranked based on differences between tumor and normal groups. Ranked genes that appear in the defined gene set are indicated as “Hits” below the Enrichment profile (black hash marks). Genes ranked near the top of the gene list are underscored with a red bar, whereas genes near the bottom of the list are underscored with a blue bar. (B) A Leading Edge Analysis comparing whether highly ranked genes corresponding to different gene sets overlapped. Highest ranked genes refer to those most highly differentially expressed genes between tumors compared to normals. Leading edge genes (i.e. those most different at level of expression between PTC tumors and normals) that correspond to highly statistically significantly enriched gene sets overlap with NRF2 transcriptional targets. These gene sets corresponded to functions related to NRF2, such as c-JUN (AP1 gene sets), a well-known transcriptional activator of NFE2L2, and BACH1 and 2, which are transcriptional repressors that compete with NRF2 to bind ARE. 100% and 0% overlap in leading edge genes are indicated by dark green and white, respectively. (C) A gene expression heatmap was generated for NRF2 transcriptional target genes that are over-expressed in PTC tumors relative to normals. Expression values for each gene are represented as colors, where the range of colors (red, pink, light blue, dark blue) shows the range of expression values (high, moderate, low, lowest).