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- Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma

Tumor microenvironmental patterns in lung adenocarcinomas
A Principal component analysis based on the proportion of stromal and immune cell clusters, color-coded by histological subtype, patients indicated. B Normalized proportion of stromal and immune cell clusters, mean module scores of tumor cell signatures, histological subtypes and mutation status per patient, patients sorted along the first principal component from principal component analysis in (A), cell clusters included in the model in (H) in bold. C Correlation of the proportion of stromal and immune cell clusters, most connected section of correlation network plot shown; Spearman’s correlation statistics, only correlations with rho > 0.7 and p < 0.05 shown. A, B, C Cell clusters occurring in <3 patients were excluded from analyses. D Number of potential paracrine interactions from microenvironmental cell clusters to tumor cells of the N³MC or CP²E pattern, computed using CellPhoneDB, grouped by interaction families, color-coded by number of interactions (see also Supplementary Fig. 10). E–G Analysis of the TCGA lung adenocarcinoma cohort. E Correlation of ssGSEA enrichment scores based on marker genes of selected microenvironmental cell clusters and tumor cell signatures; n = 533, Spearman’s correlation statistics, linear regression line. F Kaplan–Meier overall survival curves, cases grouped by the ratio of ssGSEA enrichment scores of indicated microenvironmental cell clusters or tumor cell signatures or a combined signature encompassing all cell clusters of the N³MC or CP²E pattern, respectively; n = 524, log-rank statistics. G Proportion of patients with oncogenic mutations and tumor mutational burden (TMB), patients grouped by ratio of ssGSEA enrichment scores of the combined signature in (F); n = 525 for mutations, Chi-squared test, n = 242 for TMB, two-sided Welch’s t test. H Schematic representation of subtypes of lung adenocarcinoma characterized by different grades of tumor epithelial cell differentiation and different composition of the corresponding tumor microenvironment.
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