Fig. 1

Patterns of gene expression and molecular etiologies of male and female HCC. a Sex-biased gene expression in HCC. A volcano plot of DEGs between male (N = 26) and female (N = 18) HCC tumor samples. X-linked genes are indicated in pink, Y-linked in green, and autosomal in black. Significant genes were selected based on an FDR-adjusted p-value threshold of 0.01 and absolute log₂(FC) threshold of 2. Multiple transcripts of the long non-coding RNA XIST are independently expressed. Genes that were not expressed in a sex-biased way in healthy liver (GTEx) or in the tumor-adjacent tissues are indicated with an asterisk. b An example of a gene exhibiting a sex-bias in HCC but not in healthy liver or tumor-adjacent tissues. DTX1 expression in log(CPM) is shown for male and female samples in each tissue. c A multi-dimensional scaling plot of the paired TCGA LIHC tumor and tumor-adjacent samples of each sex. Euclidean distances between samples were calculated based on 100 genes with the largest standard deviations between samples. Tissue type (dimension 1) and sex (dimension 2) drive the overall patterns of gene expression in HCC. d Venn-diagram of the overlap of DEGs in the sex-specific and combined analyses of matched tumor and tumor-adjacent samples. Substantially more DEGs were identified in the sex-specific analyses. e Sex-specific and sex-shared DEGs were analyzed for the overrepresentation of functional pathways. Sex-specific patterns of pathway enrichment point to differential processes driving the etiology of male and female HCC. f Examples of sex-specific and sex-shared pathways