Fig. 3
From: Long-term maintenance of patient-specific characteristics in tumoroids from six cancer indications
Tumoroids preserve transcriptomic features of original tumors. (a) Correlation heatmap of bulk RNA expression levels (log2(RPM + 1) levels correlated across 17,556 genes) in matched tumor tissue and tumoroids for the 20 colorectal, lung, breast, and endometrial cancer samples and tumoroids introduced in Fig. 2. Inset shows average (bar, mean ± standard deviation) Pearson’s correlation for matched tumor tissue and tumoroid pairs (dots denote unique donors) across different cancer indications. (b) Differential gene expression analysis in matched colorectal tumor tissue and tumoroids (n = 9) at fold change > 2 and false discovery rate (FDR) < 0.05. Samples analyzed are the 9 colorectal tumor/tumoroid sets shown in Fig. 2. (c) Top 10 significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of highly expressed genes in initial 9 biologically independent colorectal cancer samples (dotted line indicates FDR = 0.05). (d) Top 10 significantly enriched KEGG pathways associated with genes highly expressed in 9 derived colorectal tumoroid lines (dotted line indicates FDR = 0.05). (e) Uniform Manifold Approximation and Projection (UMAP) for dimension reduction visualization of 10,139 single cells from two matched tumor tissue/tumoroid pairs with color coded assignment of samples after single-cell RNA sequencing (scRNA-seq) for colorectal samples HuCo021320 and HuCo3209. (f) UMAP visualization with color-coded assignment of cancer cells, stromal cells, and immune cells. (g) Proportion of cell types present in initial samples (P0) and matched tumoroids (P10) for two colorectal cancer donors, HuCo021320 and HuCo3209. (h) Comparison of normalized, natural log transformed gene expression levels from pseudo-bulked scRNA-seq data of epithelial cells present in initial (P0) and tumoroid (P10) cells for HuCo3209 colorectal cells (17,731 genes) and HuCo021320 colorectal cells (17,536 genes). (i) Single cell copy number variation (CNV) plots comparing immune cells, tumor epithelial cells, and tumoroids for HuCo3209 donor. InferCNV was used to estimate CNV in epithelial cells using immune cells as the reference.
