Skip to main content
. 2021 Jun 29;12:4019. doi: 10.1038/s41467-021-24064-1

Fig. 6. In human colorectal cancers p53LOH combined with missense mutp53 shortens patient survival and upregulates HSF1 activity.

Fig. 6

ah Data from colorectal adenocarcinoma patients. COADREAD, TCGA dataset. a Tumor samples stratified for p53LOH versus no-p53LOH and grouped for either all TP53 mutations (MS missense, FS frameshift, NS nonsense) versus missense mutations-only (MS). p53LOH samples (shallow deletions) were determined by TP53 copy number alterations. Numbers in columns indicate patient numbers. b Survival curve of CRC patients harboring homozygous WT TP53 versus patients harboring missense (MS) p53 mutations plus p53LOH (shallow deletions). Number of patients and mean survival in months as indicated. Kaplan–Meier statistic, two-sided, log-rank test, p = 0.19. Note that TCGA data contains insufficient numbers of heterozygous patients (mutp53/+) with clinical data, precluding statistical survival analysis. c Heatmap of HSF1 target genes from colorectal carcinomas. Patients with homozygous TP53+/+ (WT TP53) versus patients with TP53 missense (MS) mutations plus p53LOH (MS + LOH). All genes with t test p values <0.001 were plotted as heatmap rank-ordered by their relative expression change from top to bottom. Colors represent Z-scores for each gene from blue (downregulated) to red (upregulated) expression. A homemade HSF1 target gene panel from Mendillo et al. was used46. d Correlation between HSF1 mRNA expression and p53 mutational status in colorectal carcinomas. Patients with homozygous TP53+/+ (WT TP53) versus patients with either MS/FS/NS + LOH (top, n = 435 patients) or patients with MS + LOH (bottom, n = 381 patients) with regard to their HSF1 expression. Fisher’s exact test, two-sided. e Loss of the remaining WTp53 allele correlates with high HSF1 mRNA expression in colorectal carcinomas. Patients with WT TP53 versus MS/WT (HET) versus MS + LOH. Chi-square statistic, n = 424 patients. Fisher’s exact test, two-sided, between WT versus HET and between HET versus MS + LOH. f Survival of patients with MS/NS/FS + LOH (left) or MS + LOH (right), and HSF1high versus patients with WT TP53 and HSF1low. Number of patients, mean survival in months and Kaplan–Meier statistic log-rank test, two-sided, as indicated. g, h Correlation between APC mutations and p53 mutational status (g) or mRNA expression of HSF1 and HSF1 target genes (h). Analysis as in d. Patient numbers as indicated. Fisher’s exact test, two-sided.