Fig. 1

Upstream analysis of the AK4 metabolic gene signature predicted that HIF-1α is transcriptionally activated in lung adenocarcinomas. a Genes were ranked according to their corresponding Pearson correlation coefficient (R) to AK4 expression. Genes that are positively correlated with AK4 (R ≥ 0.3) or negatively correlated with AK4 (R ≤ − 0.3) were further filtered with enzyme or transporter annotations and defined as the AK4 metabolic gene signature. b KEGG pathway analysis of the AK4 metabolic gene signature. Bar chart represents top 20 significant metabolic pathways ranked according to – log enrichment P value. P values were calculated using Fisher exact test. c GSEA plots of lung cancer prognostic, hypoxic response, and glucose metabolism genes in the AK4 metabolic gene signature. d Left, the ingenuity upstream regulator analysis algorithm predicted significant activation or inhibition of upstream regulators in the AK4 metabolic gene signature. An activation z score of more than 2 or less than − 2 was considered to indicate significant activation or inhibition, respectively. Right, a heatmap illustrating both direct and indirect HIF-1α-regulated genes that are positively or negatively correlated with AK4 expression. e Left, overall survival analysis of patients stratified according to the AK4-HIF-1α gene expression signature. Right, relapse-free survival analysis of patients stratified according to the AK4-HIF-1α gene expression signature