Extended Data Fig. 5: The ZDHHC19 gene is amplified and highly expressed in LSCC and correlated with poor clinical outcomes.
From: Fatty acids and cancer-amplified ZDHHC19 promote STAT3 activation through S-palmitoylation
a, Alteration frequency and oncoprint diagram of ZDHHC19 gene-alteration summary in patients with cancer (11,413) obtained from cBioPortal (The Cancer Genome Atlas, TGCA). b, The regions of the genome that are substantially amplified across a set of LSCC samples from TCGA were identified using GISTIC2 from Gene Pattern (Broad Institute). ZDHHC19 was confirmed as one of the genes in the amplified 3q29 region. c, Genes in the amplified 3q29 region are correlated with the STAT3 target-genes BCL2L1 and BCL2 across two datasets from the Gene Expression Omnibus (GEO) (GSE28571 (n = 100 samples) and GSE73403 (n = 69 samples)). Twenty-eight genes were analysed. P values were calculated by two-tailed Pearson correlation. d, Venn diagram of genes in the amplified 3q29 region that are significantly correlated with the STAT3 target-genes BCL2L1 and BCL2 across the two GEO datasets (GSE28571 (n = 100 samples) and GSE73403(n = 69 samples)). Thirty-six genes from the GSE28571 dataset and 30 genes from the GSE73403 datset were analysed. P values were determined by two-tailed Pearson correlation. e, The plots of P values versus q values of oncogenes that show co-occurrence or mutual exclusivity with ZDHHC19 in LSCC from TCGA (n = 501 samples). Two hundred and thirty-one genes (162 examples of co-occurrence and 69 examples of mutual exclusivity) were analysed. The P and q values were determined by Fisher’s exact test and false-discovery-rate (FDR) test, respectively. f, The plots of P values versus q values of tumour suppressors that show co-occurrence or mutual exclusivity with ZDHHC19 in LSCC from TCGA (n = 501 samples). One hundred and eighty genes (115 examples of co-occurrence and 65 examples of mutual exclusivity) were analysed. The P and q values were determined by Fisher’s exact test and FDR test, respectively. g, Gene list of oncogenes or tumour suppressors that show significant co-occurrence or mutual exclusivity with ZDHHC19 in LSCC from TCGA (n = 501 samples). The P and q values were determined by Fisher’s exact test and FDR test, respectively. h, Comparison of ZDHHC19 expression in samples from patients with LSCC or lung adenocarcinoma, obtained from the cBioPortal TCGA dataset (n = 1,097 samples). The P values were determined by two-tailed Student’s t-test. i, The expression level of ZDHHC19 in human lung-cancer cell lines was grouped into four subtypes: LSCC cell lines (lung squ) (n = 29 samples); lung large-cell carcinoma cell lines (large lung) (n = 14 samples); lung adenocarcinoma cell lines (lung adeno) (n = 53 samples); and lung small-cell lung carcinoma cell lines (small lung) (n = 53 samples). Data were obtained from Cancer Cell Line Encyclopedia database (CCLE, www.broadinstitute.org/ccle) and plotted using GraphPad Prism. P values were determined by two-tailed Student’s t-test. j, Kaplan–Meier curves of 68 patients with LSCC, after stratification by the median level of ZDHHC19, were used for depicting survival time. Patient data were derived from GSE73403 and analysed using GraphPad Prism. P values were determined by log-rank (Mantel–Cox) test. k, Kaplan–Meier curves of patients with LSCC, after stratification by the median level of ZDHHC19, were used for depicting survival time. Patient data were analysed using http://kmplot.com. P values were determined by log-rank (Mantel–Cox) test. l, Pearson analysis of gene-expression data from patients with LSCC (GSE73403 dataset (n = 69 samples)) was used for depicting the correlation between BCL2 and ZDHHC19. Data were plotted and analysed using GraphPad Prism software. m, Analysis similar to that in l; gene-expression data from patients with LSCC (GSE73403 dataset (n = 69 samples)) was used for depicting the correlation between BCL2L1 and ZDHHC19. n, Pearson analysis of gene-expression data from patients with LSCC (GSE28571 dataset (n = 100 samples)) was used for depicting the correlation between BCL2 and ZDHHC19. o, Analysis of gene-expression data from patients with LSCC (GSE28571 dataset (n = 100 samples)) was used for depicting the correlation between BCL2L1 and ZDHHC19. One hundred samples were plotted and analysed using GraphPad Prism software. In l–o, the centre line indicates a line of best fit through the data of two variables in Pearson correlation coefficient model, and the dotted lines indicate the 95%-confidence band.
