Figure 4

OXPHOS defects in benign and malignant human prostate tissue. Cells from each patient were classified based on mitochondrial protein abundance (median 14,670 cells per patient, 216,731 cells in total). (A) Mitochondrial respiratory chain (MRC) graphs depicting 500 random samples per patient and density plot including all epithelial cells across all patients within each patient group. Tissue samples from patients with no histological evidence of prostate cancer, under 45 years of age, were used as controls. Patients with benign disease were age-matched to patients with tumour tissue. (B) Proportion of cells in each abundance category stratified by individual patients. (C) Mean Z-score across all epithelial cells within 9 representative ROIs from each patient group. Mean single cell expression of NDUFB8, MTCO1 and TOMM20 across spatially disparate ranges of benign, cancerous and control prostate tissue (n = 5 patients in each group). Widespread heterogeneity both within and between patient cohorts was noted, with MTCO1-deficient cells were observed more frequently in the benign cohort, whereas NDUFB8-deficient cells were observed most frequently in a subset of patients from the cancer cohort. (D) Variation in mean Z-scores across each patient group (n = 309 ROIs from 15 patients). Note that only tumour regions from PCa patients were selected for this comparison. (E) Marker expression across tumour and benign–adjacent (BA) regions from prostate cancer patients (n = 204 ROIs from 5 patients). In panels (D) and (E), each point represents mean Z-score for all epithelial cells contained within an individual region of interest. Kruskal–Wallis test: NS, not significant; *p < 0.05; ****p < 0.0001.