Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome
Fig 3
CA20 is associated with genomic instability features in cancer.
(a) CA20 score is associated with genome doubling. Box plots of CA20 score per whole genome doubling status. **** p-value < 0.0001 (Wilcoxon rank-sum test). (b, d-f) CA20 is associated with different genomic instability features. Smooth scatter plots showing correlation between CA20 score and (b) aneuploidy score (measured as the total number of altered chromosome arms), (d) number of mutations per Mb, (e) number of CNAs and (f) clones per tumour across TCGA tumour samples (Spearman’s correlation coefficient, r = 0.44, 0.48, 0.47 and 0.43, respectively, p-value < 2.2e-16 for all). (c) Chromosome arm alterations associated with CA20 score. Volcano plot shows the results of linear regression analyses comparing CA20 score between samples with deletion or amplification of each chromosome arm. Arms whose deletions or amplifications are associated with higher CA20 (FDR < 0.05) are represented in blue and red, respectively. Chromosome arms with FDR < 1e-5 are highlighted and box plots of CA20 score per chromosome arm alteration are shown for 5q, 16p and 7p arms. **** p-value < 0.0001 (linear regression). (g) Hierarchical clustering of TCGA cancer types based on the independent association between the different genomic instability features and CA20 score. Unsupervised hierarchical clustering using Euclidean distances calculated based on multiple linear regression p-values of association with CA20 of aneuploidy score, number of mutations per Mb, number of CNAs and clones per tumour, per TCGA cohort and with all cohorts together (PanCancer). Heatmap colour scale according with -log10 of linear regression p-values. Main clusters are highlighted with different shades of grey. BLCA: bladder urothelial carcinoma; CESC: cervical squamous cell carcinoma and endocervical adenocarcinoma; GBM: glioblastoma multiforme; HNSC: head and neck squamous cell carcinoma; KIRC: kidney renal clear cell carcinoma; LGG: low-grade glioma; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; PRAD: prostate adenocarcinoma; SKCM: skin cutaneous melanoma; STAD: stomach adenocarcinoma; THCA: thyroid carcinoma.