Apart from CA9—which is known to be HIF1α-responsive and follows the increasing expression pattern of other known hypoxia-regulated genes from low to high malignancy grade breast cancer (Fig. 1E and Additional file 1: Table S4)—the other extracellular-facing, membrane-tethered carbonic anhydrases (CA4, CA12, CA14) show a consistent pattern of marked downregulation from low to high grade breast cancers (Fig. 1D and Additional file 1: Table S4). Here, CA4 is linked to breast cancer.