Fig. 2

The malignant compartment of multiple cancer types contains cells with high mitochondrial-encoded RNA content. a,b Comparison of mitochondrial RNA percentage (pctMT) between tumor microenvironment (TME) and malignant cells across 112 patients in a unfiltered cohorts and b cohorts with prior pctMT filtering in original studies (Methods) [4, 21,22,23,24,25,26, 28]. Patients with too few TME or malignant cells are discarded for this analysis. Patients with more than double the proportion of HighMT malignant cells (pctMT > 15%) compared to TME and with over 15% of HighMT malignant cells are highlighted (blue bar above boxplots). c Distribution of the dissociation-induced stress scores estimated in HighMT and LowMT malignant metacells (pctMT < 15%) across the seven studies selected for the analysis (studies with at least two samples with at least 30% of HighMT malignant metacells). A dissociation stress meta-signature is defined using the common genes in three different dissociation stress signatures [10, 11, 34]. The point biserial correlation coefficient between the score and HighMT/LowMT status is indicated over the boxplots. d,e Mean of the residuals between the experimental and predicted expression of the 13 MT-encoded protein-coding genes for the paired bulk and single-cell data from the d Wu et al. [25] and e Chung et al. [35] cohorts. The relationship between bulk and bulkified gene expression is modeled by a polynomial regression. Residuals are computed as the difference between the ground-truth and the predicted bulkified expression. We use an empirical sampling scheme where we compare the mean residuals to that of randomly sampled genes (Methods). The 95% confidence interval of the mean residuals of randomly sampled genes is represented as the shaded gray area, and significance is reported based on Bonferroni-corrected p-values. RCC: renal cell carcinoma; SCLC: small cell lung cancer; NPC: nasopharyngeal carcinoma; LUAD: lung adenocarcinoma; BRCA: breast cancer; Met. Pancr. cancer: metastatic pancreatic cancer; TME: tumor microenvironment. Significance for a–c is computed with a Mann–Whitney U test. ns: \(p>0.05\); *: \(0.01<p\le 0.05\); **: \(0.001<p\le 0.01\); ***: \(0.0001<p\le 0.001\); ****: \(p\le 0.0001\)