Fig. 7: Identification of coarse stromal subtypes in solid tumors.
a, Survival associations of per-cell-type signature genes of cytotoxic lymphocyte subsets. Top, bar plot illustrating the pan-cancer survival association across 23 cancer types, aggregated across malignancies using Stouffer’s method. Columns are ordered by combined z score. Bottom, cancer-specific survival association determined by the Cox proportional hazards model; LUSC, lung squamous cell carcinoma; COAD, colon adenocarcinoma; READ, rectum adenocarcinoma; LUAD, lung adenocarcinoma. b, Survival associations of per-cell-type signature genes in myeloid subsets; SARC, sarcoma. c, Survival associations of per-cell-type signature genes in fibroblast subsets. d, Heat map of 8,743 individuals from TCGA classified into four distinct TME subtypes based on clustering of the signature of all cell types; Bn, naive B cells; Bm, memory B cells; Bgc, germinal center B cells. e, Box plot illustrating the cytotoxic signature scores of ecotypes, including lymphocytes, calculated from 8,734 samples from the TCGA project. Statistical significance was evaluated using two-tailed unpaired Wilcoxon tests combined with a permutation test (10,000 resamplings) to compare the signature score distribution across pairwise ecotypes; horizontal connectors denote compared groups, with the corresponding P value indicated above the horizontal line. The bottom of the box represents Q1, whereas the top represents Q3. The height of the box indicates the IQR, and the horizontal line inside the box represents the median. The whiskers extend to the positions of Q1 – 1.5 × IQR and Q3 + 1.5 × IQR. f, Box plot comparing tumor purity across different tumor ecosystem groups, calculated from 8,734 samples from the TCGA project. The bottom of the box represents Q1, whereas the top represents Q3. The height of the box indicates the IQR, and the horizontal line inside the box represents the median. The whiskers extend to the positions of Q1 – 1.5 × IQR and Q3 + 1.5 × IQR. g, Box plot comparing CD8+ T cell infiltration of individuals stratified by tumor ecosystem groups. CD8+ T cell infiltration was estimated using QUANTISEQ from 8,734 samples from the TCGA project. The bottom of the box represents Q1, whereas the top represents Q3. The height of the box indicates the IQR, and the horizontal line inside the box represents the median. The whiskers extend to the positions of Q1 – 1.5 × IQR and Q3 + 1.5 × IQR. h, Bar graphs depicting the segregation of each carcinoma into the five tumor ecosystem groups. i, Kaplan–Meier curves illustrate the overall survival analysis of five tumor ecosystem groups across 459 individuals with SKCM and 1,091 individuals with BRCA; +, censored observations. Statistical significance was assessed via the log-rank test, with P values of 2.54 × 10−5 for SKCM and 0.0229 for BRCA.
