Fig. 5: Tumour-cell phenotypes and microenvironment remodelling in the context of WGD. | Nature

Fig. 5: Tumour-cell phenotypes and microenvironment remodelling in the context of WGD.

From: Ongoing genome doubling shapes evolvability and immunity in ovarian cancer

Fig. 5: Tumour-cell phenotypes and microenvironment remodelling in the context of WGD.

a, Scatter plot depicting GEE regression coefficients versus Benjamini–Hochberg-adjusted P values for selected genes and pathways in WGD-high and WGD-low tumour cells. MHC, major histocompatibility complex. b, Per-sample mean gene expression of STING1 in WGD-high (n = 63) and WGD-low (n = 34) samples. Centre line shows the median, box boundaries show quartiles and whiskers indicate 1.5 × IQR. Significance calculated using two-sided Wilcoxon rank sum test is included. c, Scatter plot of STING1 gene expression versus rate (counts per cell) of chromosomal losses, split by WGD-low and WGD-high (colours). Lines indicate the result of a linear regression in either WGD-high or WGD-low tumours. Regression coefficients and significance results are shown separately for WGD-low and WGD-high tumours. d, Example immunofluorescence images of WGD-high and WGD-low tumour samples with varying STING1 expression. Top, multichannel overlay images of STING1, panCK, DAPI and cGAS intensity at high magnification (scale bars, 125 μm). Bottom, zoomed insets (locations indicated by white boxes in the top panels; scale bars, 15 μm). e, Boxplots showing distribution of per-sample mean STING1 immunofluorescence intensity over tumour cells for WGD-high and WGD-low samples. Box plots are defined as in b. Significance calculated using a GEE model is included. f, Scatter plot and density estimation of STING1 versus micronuclei rate for 1 mm × 1 mm tiles in tumour ROIs. Points, density contours and coefficients, and P values of a generalized linear model are coloured by WGD-high and WGD-low tumour status. g, Differential cell-type abundance testing results from Milo with permutation testing (Methods) for cell types in WGD-high versus WGD-low samples. h, Normalized enrichment scores (NES) in the interferon pathway for cell types in the tumour microenvironment. CAF, cancer-associated fibroblasts; cDC1, conventional type 1 DCs; DCs, dendritic cells; EC, endothelial cells; NK, natural killer; pDC, plasmacytoid DCs. i, NES in the cell-cycle pathway for cell types in the tumour microenvironment.

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