Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome
Fig 4
CA20 is associated with cancer’s mutational spectrum.
(a) Somatic mutations pan-cancer-wide associated with the CA20 score. The volcano plot shows the results of linear regression analyses comparing the CA20 score between mutated and wild-type samples for 14,589 genes (at least 20 mutated samples). Genes whose mutations are associated with higher and lower CA20 (FDR < 0.05) are represented in red and blue, respectively. The top 10 genes are highlighted. (b) TP53 mutations are associated with CA20 in different cancer types. Linear regression coefficients, representing CA20 score differences between TP53 mutated and wild-type tumour samples, across TCGA cohorts with at least 20 mutated samples. Significant associations (FDR < 0.05) are coloured as in (a). (c) Mutational signatures pan-cancer-wide associated with CA20, independently of other types of genomic instability. Left: Significance of linear regression analyses (-log10 p-value) between CA20 and contribution of each mutational signatures including, as independent variables, the four genomic instability features: aneuploidy, mutation burden, CNA and number of clones per tumour. Positive and negative significant associations (FDR < 0.05) are coloured in red and blue, respectively. Right: Smooth scatter plots showing correlations between CA20 and the contribution of mutational signature 1 (linked with ageing) in 3 TCGA cohorts. Linear regression p-values are shown. (d) Causal effect of CA20-associated mutations on CA20 levels. Scatter plot of linear regression’s coefficient from (a) versus Connectivity Map (CMap)’s knock-down score, ranging from 100 (CA20 up-regulation) to -100 (CA20 down-regulation), for each gene in common. Genes are coloured as in (a) and the ones with both significant linear regression associations and absolute knock-down score higher than 80 are highlighted. (e and f) Gene Set Enrichment Analysis (GSEA) of genes ranked by their CMap’s knock-down score using (e) a manually curated list of centriole duplication factors and (f) MSigDB’s Hallmark Gene Sets (unfolded protein response and mitotic spindle were significantly associated, FDR < 0.05). GSEA p-values are shown. BLCA: bladder urothelial carcinoma; BRCA: breast invasive carcinoma; CESC: cervical squamous cell carcinoma and endocervical adenocarcinoma; ESCA: oesophageal carcinoma; GBM: glioblastoma multiforme; HNSC: head and neck squamous cell carcinoma; KICH: kidney chromophobe; LGG: low-grade glioma; LIHC: liver hepatocellular carcinoma; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; OV: ovarian serous cystadenocarcinoma; PAAD: pancreatic adenocarcinoma; PRAD: prostate adenocarcinoma; SARC: sarcoma; SKCM: skin cutaneous melanoma; STAD: stomach adenocarcinoma; UCS: uterine carcinosarcoma.