Fig. 4: Comparison of dynamics of immune-related gene expression and genomic analyses in major and minor responders.
Baseline samples were available in 7 major responders and 21 minor responders. Post-chemotherapy samples were available in 6 major responders and 10 minor responders. Surgery resection samples were available in 4 major responders and 18 minor responders. a–d single sample scoring of four genesets using singscore85. (*) indicates p < 0.05 by two-sided paired Wilcoxon test, not corrected for multiple testing. P-values: a baseline vs surgical resection: 4.5 × 10-5; b baseline vs surgical resection: 1.5 × 10-5; post-induction chemo vs surgical resection: 0.016. e, f normalized expression level of PD-1 and PD-L1 in each sample. (*) indicates p < 0.05 by two-sided paired Wilcoxon test, not corrected for multiple testing. P-values: e baseline vs surgical resection: 6.7 · 10-3; post-induction chemo vs surgical resection: 0.031; f baseline vs surgical resection: 5.6 · 10-3. g, h immune cell type abundance estimate obtained through the average expression of marker genes from Danaher et al.88. (*) indicates p < 0.05 by two-sided paired Wilcoxon test, not corrected for multiple testing. P-values: g baseline vs post-induction chemo: 2.0 × 10-3; baseline vs surgical resection: 0.045. i Mutational load as estimated by the number of somatic variants per million basepairs. Two-sided Wilcoxon test p = 0.075. j Homologous recombination deficiency signature score based on the number of large-scale state transitions in the genomic copy number profile as described in the study of Popova et al.97. Only the baseline whole exome sequencing samples were used (major responders: n = 8 and minor responders: n = 20). Horizontal gray lines indicate ploidy-specific cutoffs indicative of homologous recombination deficiency. Points are colored by BRCA1 gene mutational status, where ‘pathogenic’ BRCA1 mutations are clinically established pathogenic variants, and ‘functional damaging’ indicates a BRCA1 variant that has been found to be damaging based on three functional tests98, but has not yet been proven to be pathogenic and is clinically a variant of uncertain significance. No BRCA2 mutations were found in this cohort. Source data are provided as a Source Data file.
