When the extracellular concentration of acidic respiratory end-products is lower than intracellular, the excess CO2 can passively across the cell membrane by diffusion.47 However, in most cases, the CO2 and lactate generated from glucose metabolise is accumulated in extracellular tumour site due to low blood flow rate, resulting in development of acidic microenvironments in tumour.48,49 In this situation, the release of CO2 and lactate in microenvironments mainly relies on numerous special membrane proteins, such as carbonic anhydrase enzymes (CA2, CA9 and CA12). This evidence concerns the gene CA2 and neoplasm.