Since 15-PGDH is an NAD+ −dependent enzyme and NAD+ levels are significantly reduced in central tumour regions and hypoxic tumour cells, inefficient 15-PGDH enzyme function due to NAD+ depletion in hypoxia may explain the paradoxical finding of increased PGE2 levels in central regions of CRCLM in the presence of higher 15-PGDH protein levels. The gene discussed is HPGD; the disease is neoplasm.