Fig. 6: MIRO2 is overexpressed at the leading edge of SCCs.
a, Dot plot showing expression of mitochondrial trafficking genes; violin plot showing expression of MIRO2 in different cell types in SCCs (n = 5,799 myeloid cells, 4,644 tumor cells, 1,495 epithelial cells, 584 fibroblasts, 413 lymphoid cells, 169 endothelial cells and 129 melanocytes). b, Violin plot showing expression of MIRO2 in tumor cell subpopulations in SCCs based on scRNA-seq data40 (n = 296 tumor-specific keratinocytes (TSKs), 1,385 basal tumor keratinocytes (KC), 725 cycling tumor keratinocytes and 2238 differentiating tumor keratinocytes). c, Feature plots showing spatial distribution of MIRO2 transcripts in human skin SCC; violin blots showing MIRO2 transcripts at the tumor leading edge versus the total tumor and its microenvironment (TME) (n = 2 tumors from different patients; P2 and P6)40. d, Western blot of lysates from HPFs, HaCaT, HaCaT-Ras and A431 cells for MIRO2 and GAPDH. e, MIRO2 and K14 immunofluorescence stainings of sections from 3D organotypic skin cultures with HPFs and HaCaT or A431 cells and quantification of the MIRO2-positive area (n = 3 3D cultures per epithelial cell line). Scale bar, 100 μm. f, Forest plot showing the 5-year disease-specific survival (DSS) associated with MIRO2 expression across solid cancers based on TCGA. Hazard ratios (HRs) and 95% confidence intervals (CIs) based on Cox proportional hazard model are shown. The last point represents the estimate from the random-effects meta-analysis (n = 8,941 patients). g, Pearson correlation coefficient (ρ) and 95% CIs between the enrichment score of the leading edge (LE) signature and MIRO2 expression across the different solid cancers in TCGA. The last point represents the estimate from the random-effects meta-analysis (n = 10,238 patients). h, Dependency of different cancers on MIRO2 expression as documented in the DepMap Portal. Gene effect scores are derived from DEMETER2 or CERES. A lower score denotes a greater dependency on expression. Violin plots in a–c show the median (center line), 25th and 75th percentiles (box bounds) and whiskers extending to the most extreme data points within 1.5 times the interquartile range from the box. Points outside this range are plotted as outliers. The graph in e shows the mean ± s.e.m. A Mann–Whitney U-test for comparison between two groups (a,b) or unpaired two-sided Student’s t-test (e) was used to determine statistical significance.
