Fig. 8: EGFR TKI-resistant NSCLC patients show high deNG-IL6 expression and a shift signaling preference from JAK-STAT3 to the SRC-YAP axis.

a Pattern of secreted IL6 in MPECs derived from MPE of EGFR-TKI-naïve (TN01-TN04) and EGFR-TKI-resistant (TR01-TR05) patients as detected by WB (n = 1). b N-glycosylated IL6 detected by lectin blotting with WGA (n = 1). c Percentage proportions of NG-IL6 and deNG-IL6 in the CM of EGFR-TKI-naïve and EGFR-TKI-resistant MPECs (n = 1). d GSEA enrichment plot showing genes related to the N-glycosylation process derived from transcriptome data for patient tumors before and after the development of osimertinib resistance⁵⁸ named OSTu and ORTu, respectively. Sequential process by which 15 patients were selected according to the indicated criteria (left panel). The right panel shows the GSEA enrichment plots for N-glycosylation signature genes (right panel, top) and heatmaps for the enrichment scores (right panel, bottom) of selected patients (determined by Morpheus). Nominal p-value was one-tailed test on the appropriate side of the null distribution. e Expression and intracellular location of STAT3 and SRC in paired lung cancer tissues from six NSCLC patients (TKI_01-TKI_06) before (TKI-naïve) and after development of resistance (TKI resistant) to EGFR TKI as determined by TissueFAXS-imaged IF (see also Supplementary Fig. 28 for H&E staining). The paired tissues from the same patient were attached to the same slide to perform IF staining. Images are selected magnified region from the full tissue. Scale bars, 20 μm. f Expression of nuclear STAT3 and membranous SRC as quantified by TissueQuest. Source data are provided as a Source Data file.