Fig. 4: Upregulated PRC2⁺- and PRC2⁻–CGI genes control distinct sets of biological pathways in cancer.

a, b Hallmark pathway enrichment results for (a) upregulated PRC2⁺-CGI genes and (b) upregulated PRC2⁻-CGI genes. “EMT” and “Estrogen response early” are highlighted in the two breast cancer subtypes. For a, b the one-sided binomial-test was performed on these two groups and the enriched hallmarks with unadjusted p-value < 0.05 were identified. c Expression of the 10 BasalBRCA upregulated PRC2⁺-CGI genes in the EMT pathway are shown in 13 BasalBRCA cell lines annotated by an established consensus EMT classification (see text). d IGV plots for the top 3 EMT genes from panel c. e siRNA loss-of-function assays for the top three genes followed by expression measurement of established mesenchymal markers. n = 3 biologically independent experiments. Data are presented as mean ± SD. p-values were determined by a one-sided t-test. p < 0.001***; p < 0.01**; p < 0.05*. The exact p-values are shown in Supplementary Data 4. f Average expression of CD8 + T-cell signature genes in the six cancer types enriched in the inflammatory response pathway from panel a, showing the top and bottom 20% of tumors based on the average expression of upregulated PRC2⁺-CGI genes in the inflammatory response pathway. Signature A contains CCL2, CCL3, CCL4, CXCL9, CXCL10, CD8A, HLA-DOB, HLA-DMB, HLA-DOA, GZMK, ICOS and IRF1³⁶. Signature B contains GZMA and PRF1³⁷. p-values were determined by a one-sided t-test. p < 0.001***; p < 0.01**; p < 0.05*; p > 0.05, ns. The exact p-values are shown in Supplementary Data 4. Expression datasets were obtained from TCGA. We only showed cancer types where the pathways were enriched with a p-value < 0.05. The total tumor sample sizes with expression data in different cancer types are listed in Supplementary Table 1 and the top and bottom 20% of tumor samples in each cancer type were used. g The average expression of upregulated PRC2⁺-CGI genes in the inflammatory response pathway in KIRC patients with differential response to immune checkpoint therapies. Expression datasets are obtained from Miao et al.³⁸. p-value was determined by a one-sided t-test. Box plots in (f, g) indicate the median (middle line), 25th, 75th percentile (box) and 5th and 95th percentile (whiskers). h Kaplan–Meier survival plot analyzing the average expression of upregulated PRC2⁺-CGI genes in inflammatory response pathway using the same cohort of KIRC patients.