Fig. 5: RESIST-M gene signature derived from oxaliplatin-resistant models is specifically enriched in the CMS4 subtype of colorectal cancer patients.

Expression of RESIST-M1 and M2 genes in TCGA-COADREAD (n = 377) (A, B) and PETACC-3 dataset (n = 604) (C, D). Mean expression of gene signatures reported for oxaliplatin resistance from Yin et al. E and Lin et al. F in TCGA-COADREAD dataset. G Heatmap showing publicly available bulk RNA-seq data from Singapore colorectal cancer patients (n = 162, SG-BULK, ID: syn26720761) with RESIST-M signature. Patients with high expression of both SERPINE1 and SMARCD3 and low expression of SC5D, FDPS, MVD, HMGCS1, HMGCR, CYP51A1, and ACAT2 are enriched in patients of a CMS4/iCMS3-fibrotic subtype. Each column denotes data on a single CRC patient, and each row indicates the patient subtype based on available clinical data and z-scored values based on RESIST-M, Lin et al., Yin et al., RCC, RPS gene expression from top to bottom. Seven of the twelve genes from the RCC gene were used in this analysis which includes stromal genes (INHBA, BGN, FAP), cell cycle genes (MKI67, MYC, MYBL2) and GADD45B. RPS gene score includes mean expression of four DNA repair genes- RIF1, XRCC5, PARPBP, and RAD51. Clinical data shown in the legend include patient subtype based on either iCMS, CMS, TGFBR2 mutation, iCMS-microsatellite (iM), or iCMS-fibrosis status (iF). Kaplan Meier curves for overall survival of CRC patients in TCGA COADREAD dataset stratified using RESIST-M1 (H), RESIST-M2 (I), Yin et al. (J), Lin et al. (K), RCC (L), RPS (M) gene signatures. Statistical significance for A–F was determined using Wilcoxon rank-sum test, and log-rank p test was done for H–M. * represents a p value of <0.05, ** represents <0.01, **** represents <0.001.