Lastly, the higher HIF-1α expressions under hypoxic regions are positively correlated with higher p53 expressions both in the patients with ESCC and EAC compared to those under normoxic regions [48], which are associated with upregulated TIGAR by HIF-1α in metabolic changes of the tumor microenvironment and therapy sensitivity [49]. This evidence concerns the gene HIF1A and esophageal squamous cell carcinoma.