Fig. 1

Schematic diagram of the study design and development of gene signatures. A liver cancer cohort (GSE14520) was used to define the first 45-gene signature. Briefly, 79 tumor-infiltrating T-cell genes were identified as HIF targets using a HIF-1α/2α ChIP-seq dataset. Of these 79 genes, 26 genes were > 1.5-fold upregulated in GSE14520. Independently, 23 hypoxia genes were identified as HIF targets. Uniting the 23 hypoxia-HIF genes and 26 T-cell-HIF genes resulted in 45 unique genes representing the first gene signature. Cox regression analyses of individual 45 genes in each of the three liver cancer cohorts (GSE14520, TCGA-LIHC and LIRI-JP) revealed a common prognostic set consisting of 8 genes that represent the second signature. This 8-gene signature is further validated in liver and five other cancers using Kaplan–Meier, Cox regression and receiver operating characteristic analyses