Fig. 8: The p-IWS1/U2AF2 pathway is active in human lung adenocarcinomas and impacts tumour grade, stage, metastatic potential and treatment relapse in patients with EGFR mutant, but not KRAS mutant tumors. | Nature Communications

Fig. 8: The p-IWS1/U2AF2 pathway is active in human lung adenocarcinomas and impacts tumour grade, stage, metastatic potential and treatment relapse in patients with EGFR mutant, but not KRAS mutant tumors.

From: RETRACTED ARTICLE: AKT3-mediated IWS1 phosphorylation promotes the proliferation of EGFR-mutant lung adenocarcinomas through cell cycle-regulated U2AF2 RNA splicing

Fig. 8

a Lysates of 30 LUAD samples paired with NAT, and 10 unpaired samples, were probed with the indicated antibodies. RT-PCR of U2AF2 in the same samples was performed, using exon 1 and 3 primers. Bars show the U2AF2 E2/E3 exon ratio in the tumors in the upper panel, relative to the average of the 30 normal samples. b Correlation heatmaps between components of the IWS1 phosphorylation pathway, in the LUADs in a. Correlation coefficients were calculated using simple linear regression. The values and the statistical confidence of all the comparisons can be found in Supplementary Table 5. c Violin plots showing the abundance of IWS1 phosphorylation and the U2AF2 E2/E3 ratio (right) in stage I and Stage II/III tumors. Data shown for all tumors in panels a and b, and selectively for EGFR or KRAS mutant tumors. The horizontal black lines indicate mean values for phospho-IWS1 levels and U2AF2 E2/E3 ratios. Statistical analyses were performed using the one-sided unpaired t-test. d Kaplan-Meier Curves of phosphor-IWS1 and U2AF2 E2/E3 ratios in the LUAD cohort in panel a. Statistical analyses were performed using the one-sided log rank test and Cox’s proportional hazards model. e Heat Maps showing the correlation of IWS1 or SRSF1 with components of the IWS1/U2AF2 pathway in the TCGA LUAD database using log2 normalized counts. f Heatmaps showing the expression of IWS1 pathway components in the tumors of the GSE13213 dataset. g (Left panel) Heat Maps showing expression of IWS1 pathway components in resected brain metastases and primary lung adenocarcinomas. RNA-seq data for metastatic lesions were derived from the GSE141685 dataset and for primary LUADs from TCGA. (Right upper panel) scRNA-Seq data from GSE123903. Force-directed layout/t-SNE of all metastatic tumor cells isolated from patient-derived mouse xenografts (Laughney et al., 202071), colored by source, (Right lower panel) Force-directed layout (as in the upper panel) of all xenograft tumor cells colored for z-normalized IWS1 and CDCA5 expression. h Kaplan–Meier curves showing the impact of IWS1, U2AF2 E2/E3 and FGFR2 IIIb/IIIc ratios on patient survival in the indicated patients in the TCGA LUAD database. Statistical analyses were performed as in panel d.

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