Fig 2: The transcription levels of BIRC5 in lung cancer. (A) The expression level of BIRC5 in different cancers compared with that in normal tissues in the Oncomine database (P<0.0001, |FC|>2, and gene ranking of all). Compared with normal samples, BIRC5 mRNA was overexpressed in lung cancer samples in the Oncomine database (B) and UALCAN database (C, D) ***P < 0.001. (E) Immunohistochemical staining of BIRC5 protein expression in normal lung tissue and NSCLC tissue was obtained from the Human Protein Atlas online database (magnification, ×40).

Fig 3: HSD17B6 reduces radioresistance in lung cancer cells.A–C GSEA analysis revealed that HSD17B6 expression levels were negatively correlated with gene signatures of “HALLMARK DNA REPAIR” and “HALLMARK UV RESPONSE UP” in TCGA LUAD, GSE68465, and GSE72094 datasets. D Protein levels of Ku70, Ku80, and Survivin were assessed by western blotting after HSD17B6 overexpression. E–G Correlation analysis of HSD17B6 expression and expression of DNA repair/survival-related genes (XRCC6, XRCC5, and BIRC5) in TCGA LUAD, GSE68465, and GSE72094 datasets. H Clonogenic survival of H1299 and H1975 following radiation. I Cell survival curves of H1299 OE-NC (blue line) and H1299 OE-HSD17B6 cells (red line) were plotted by the multi-target single-hit model. J Cell survival curves of H1975 OE-NC (blue line) and H1975 OE-HSD17B6 cells (red line) were plotted by the multi-target single-hit model.

Fig 4: The CXCR4-LASP1-eIF4A/B Axis is Upregulated in Breast Carcinoma Patients. Gene expression data was obtained and analyzed using Oncomine.com. Two representative datasets were selected. Box and whisker plots of the log2 median centered ratio (fold change) are shown for each. (A) Radvanyi Breast Invasive Ductal Carcinoma (n = 31 for CXCR4, LASP1, eIF4A, and CCND1. n = 28 for BIRC5 and ROCK1. n = 27 for MDM2) vs. Breast Tissue (n = 9 for CXCR4, LASP1, eIF4A, and CCND1. n = 2 for BIRC5. n = 5 for MDM2 and ROCK1). (B) Radvanyi Breast Invasive Lobular Carcinoma (n = 7 for CXCR4, LASP1, eIF4A, and CCND1. n = 2 for BIRC5. n = 6 for MDM2 and ROCK1) vs. Breast Tissue (n = 9 for CXCR4, LASP1, eIF4A, and CCND1. n = 2 for BIRC5. n = 5 for MDM2 and ROCK1). (C) TCGA Breast Invasive Ductal Carcinoma (n = 389) vs. Breast Tissue (n = 61). (D) TCGA Breast Invasive Lobular Carcinoma (n = 36) vs. Breast Tissue (n = 61). * Indicates p < 0.05 as evaluated by student's t-tests.

Fig 5: The expression of SURVIVIN depends upon Trp53R172H status. (A) GSEA reveals enrichment of the YAP signature in Trp53R172H/− shCtrl-M cells. (B) RNA-seq shows that BIRC5, a YAP target gene, is increased significantly in Trp53R172H/− shCtrl-M cells. (C) QRT-PCR of BIRC5 confirms its up-regulation in Trp53R172H/− shCtrl-M compared with shTrp53-M cells. Trp53R172H/− shCtrl-M (n = 5) versus shTrp53-M (n = 3), P = 0.0287, unpaired t-test. Error bars represent SEM. (D) Immunohistochemical staining of SURVIVIN in 3D organoids form by Trp53R172H/− shCtrl and shTrp53 cells. Trp53R172H/− shCtrl (n = 10 organoids) versus shTrp53 (n = 14 organoids), P = 0.016, unpaired t-test. Error bars represent SEM. Scale bar, 100 µm. (E) Immunohistochemical staining of p53 (top) and SURVIVIN (bottom) in the esophagus epithelium of Trp53R172H/− andTrp53−/− mice treated with 4NQO. P53 staining: Trp53R172H/− versus Trp53−/−, n = 8 each group. (*) P = 0.0168, unpaired t-test. SURVIVIN staining: Trp53R172H/− versus Trp53−/−, n = 8 each group. Error bars represent SEM. Scale bar, 100 µm. (F) Immunohistochemical staining of SURVIVIN in Trp53R172H/− shCtrl and shTrp53 in metastatic lung lesions. Trp53R172H/− shCtrl (n = 15 tumors) versus shTrp53 (n = 10 tumors), P = 0.0178, unpaired t-test. Error bars represent SEM. Scale bar, 100 µm.