The Genomic Analysis of Lactic Acidosis and Acidosis Response in Human Cancers
Figure 5
Lactic acidosis directs toward aerobic respiration by inhibiting the expression of glycolytic genes (A,B).
The contribution of aerobic respiration and glycolysis to ATP generation under control, lactic acidosis and hypoxia is measured by the degree of inhibition of ATP generation after treatment of rotenone (A) and 2-DG (B) at the indicated time after treatment. (C) The amount of ATP generation at different time points under the indicated conditions. (D) The genes in the glycolysis pathways were up-regulated by hypoxia and down-regulated by lactic acidosis. (E) The expression of genes listed as “glycolysis pathway” was extracted and clustered. (F) The mean expression values of the 53 glycolysis genes for each HMEC under hypoxia, lactic acidosis and hypoxia/lactic acidosis are calculated and shown. (G)(H) The expression of genes in the glycolytic pathways under hypoxia and lactic acidosis were used to predict the pathways activity and stratified the indicated breast cancer samples. This small set of genes recapitulated the result using the whole lactic acidosis and hypoxia gene signatures. (I) Scatter plots showing the relationship between the probability of hypoxia response (Y-axis) and lactic acidosis response (X-axis) for genes in the glycolysis pathways. Each point in the scatter plots represents a single tumor from the indicated breast cancer data sets. The probability (p) between hypoxia and lactic acidosis signatures across all samples in the indicated data set is shown.