We identified eight significantly mutated genes, of which six are well known tumour-associated genes (TP53, RB1, CDKN2A, PIK3CA, NOTCH1, NFE2L2), and two have not previously been described in ESCC (ADAM29 and FAM135B).
Our team found the expression of Nrf2 correlated with the lymph node metastasis of esophageal squamous cell carcinoma by pathological sections of esophageal carcinoma patients.
Mutations were validated in several genes, including in TP53, CDKN2A, FAT1, NOTCH1, PIK3CA, KMT2D and NFE2L2, which had been previously implicated in ESCC.
Mutations in TP53 and CDKN2A and copy number alterations in 11q (contains CCND1), 3q (contains SOX2), 2q (contains NFE2L2), and 9p (contains CDKN2A) were considered to be trunk variants; these were dominant mutations detected at high frequencies in clones of paired IEN and ESCC samples.
Furthermore, <i>miR-432-3p</i> was overexpressed in primary ESCC tumors (55 of 84, 65.5%) and a negative correlation between the expression level of KEAP1 and <i>miR-432-3p</i> in primary ESCC tumors was observed.<b>Implications:</b> These findings provide novel insights into the mechanism of NRF2 stabilization in human cancers.<i></i>.
Positive Nrf2 expression in the nucleus was of diagnostic value for predicting ESCC from normal esophageal mucosae, and was significantly associated with poorer clinical response and poor progression-free survival after CRT.
Blocking glycolysis transiently inhibits cell proliferation and may therefore have therapeutically beneficial effects on NRF2<sup>high</sup> ESCC in humans.