Figure 10. Stromal contributions and potential therapeutic agents.
(A) Schematic diagram showed the PDX transcriptome is a mixture of human RNAs (deriving from cancer cells) and mouse RNAs (deriving from stromal cells). (B–C) Transcriptional classification of paired human CRC samples and PDX derivatives in Uronis cohort (B) and Isella cohort (C). (D) Transcriptional classification of paired samples before and after radiotherapy. (E) UMAP projected all cells annotated by reference component analysis (RCA) in spatial distribution. (F) Identification of potential therapeutic agents for six subtypes. (G) The distribution of HRD score and HRD pathway mutations among six subtypes. Kruskal-Wallis test.
Figure 10—figure supplement 1. Stromal contribution to the subtype transitions.
(A) Fractions of subtype-discriminant genes of the PAM classifier belonged to stromal genes. (B–C) The cell distribution of 11 patients (B) and GINS subtypes (C) according to the two-dimension UMAP analysis. (D) The composition of cells in each subtype.
Figure 10—figure supplement 2. Clinical significance of six subtypes in GSE56699.
(A) Kaplan-Meier curves of overall survival for six GINS subtypes across all treated samples. (B) The distribution of CAF score in six subtypes. (C) Kaplan-Meier curves of overall survival for high and low CAF groups across GINS2 samples. (D) The distribution of radiotherapeutic non-responders in six subtypes.
Figure 10—figure supplement 3. Identification of potential therapeutic agents for six subtypes.
(A) Overview of the analysis procedures. (B) Transcriptional classification of paired samples before and after purification. (C) Comparison of estimated drug sensitivity (logAUC) between KRAS mutant and wild type group. **p<0.01, ***p<0.001, ****p<0.0001.
Figure 10—figure supplement 4. Candidate agents of six subtypes.
Score represents the normalized drug sensitivity (logAUC).