Figure 1.
Workflow of the present study. A total of 398 COAD and READ RNA-seq profiles from 398 donors of TCGA with complete clinical information. We used a likelihood-ratio test followed by statistical adjustment for sex, age, T stage, N stage, and M stage to determine the genes whose expression was significantly affected by TNM stage progression. We then used the single-cell RNA sequence data (scRNA-seq) that characterized the immune and stromal cell populations of colorectal cancer [Zhang et al. (19), GSE146771] to identify the tumor microenvironment cell types that normally express these stage-related genes. Finally, the different expression between the transcriptome profiles of pre- and post- ICI treatment were compare in a pMMR colorectal cancer patient. The ICI response-related genes were then identified and cross-referenced with stage-related genes to determine the gene set that predicts ICI response in treatment-naive patients. COAD, colon adenocarcinoma; READ, rectal adenocarcinoma; pMMR, mismatch repair-proficient; ICI, immune checkpoint inhibitors; NS, not significant.