IL-6/STAT3 pathway is augmented in ER + ILC compared to ER + NST tumors. (A, B) Expression of IL6 (A) and pSTAT3 (B) in TCGA RNAseq and RPPA dataset, ER + ILC (n = 191) and ER + NST (n = 555). (C) Enrichment of “Hallmark IL6 JAK STAT3 signaling” in ER + ILC following GSVA of TCGA RNA-Seq dataset. (D) ESTIMATE stromal scores (NST n = 332, ILC n = 120). E-G Spearman correlation of ESTIMATE stromal score with IL6 (E), STAT3 (F) and pSTAT3 (G) expression in ER + ILC tumors (RNAseq data n = 120, RPPA data n = 80). (H) Fold change of IL6 expression in stroma compared to tumor epithelial compartment in laser capture microdissection data for NST (n = 34, GSE68744) and ILC (n = 17, GSE148398). (I) Expression of IL6 in the stromal compartment of ER + NST (n = 412) and ER + ILC (n = 63) determined by RNAscope, p = 0.008. (J) Expression of nuclear STAT3 in the tumor compartment of ER + tumors (NST n = 332, ILC n = 39), p = 0.019. Unpaired two-tailed (A and D) t-test and (B, C, H) Mann-Whitney tests in GraphPad Prism, * p < 0.05, ** p < 0.01, **** p < 0.0001. (I-J) two-tailed Mann-Whitney U tests in SPSS. K Spearman correlation between stromal IL6 and tumoral nuclear STAT3 in ER + ILC tumors (n = 35). All correlation analysis carried out in GraphPad Prism
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