Fig. 7: Transcriptome profile of mt-related genes.

Differential mRNA expression of mitochondrial genes and enriched metabolic KEGG pathways were analyzed in 16 paired tissue samples representative for the sample cohort. a Respiratory characteristics of tissue samples for which RNA-seq expression analysis was performed. The effects of the substrates glutamate&malate, pyruvate, succinate, of oxidative stress, uncoupler FCCP, and CI inhibitor rontenone on O₂ flux in benign (blue, N = 16) and malignant (red, N = 16) tissue samples are shown. Data are presented as mean values ± SD. Differences were tested for significance using Wilcoxon signed-rank test. b Heatmap and hierarchical clustering of all significantly differentially expressed mt-related genes (FDR < 0.01) based on the MitoCarta 2.0 Gene Catalog in the benign (blue) or malignant (red) tissue samples. c Enriched metabolic KEGG pathways upregulated (red) or downregulated (blue) in cancer tissue based on the InnateDB pathway overrepresentation analysis of all differentially expressed mt-related genes. d Boxplots representing Fragments Per Kilobase Million (FPKM) values for expression of significantly increased metabolic key-enzymes in the malignant (red, N = 16) vs the benign (blue, N = 16) tissue samples. Data are presented as boxplots with median, 25th–75th percent percentile (box), minimum and median ± 1.5 IQR (whiskers) and minimum and maximum values (dots). Differences were tested for significance using multiple t-test followed by Benjamini–Hochberg correction for multiple testing. e Detailed annotation of single upregulated TCA-cycle key-enzymes in the benign (blue arrows) and malignant (red arrows) samples. Blue boxes mark steps mainly involved in NADH-linked electron transfer, orange boxes highlight steps related to succinate-linked electron transfer, and green boxes mark steps involved in ROS detoxification. Substrates used during the respirometry experiments are indicated in bold type while blue or red colored names and arrows mark enzymes and enzymatic reactions that are higher in either benign or malignant samples, respectively. Full names of enzymes are given in the main text. Source data are provided as a Source Data file.