An immune-related gene prognostic index for predicting prognosis in patients with colorectal cancer

Colorectal cancer (CRC) is one of the most common solid malignant burdens worldwide. Cancer immunology and immunotherapy have become fundamental areas in CRC research and treatment. Currently, the method of generating Immune-Related Gene Prognostic Indices (IRGPIs) has been found to predict patient prognosis as an immune-related prognostic biomarker in a variety of tumors. However, their role in patients with CRC remains mostly unknown. Therefore, we aimed to establish an IRGPI for prognosis evaluation in CRC.

RNA-sequencing data and clinical information of CRC patients were retrieved from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) databases as training and validation sets, respectively. Immune-related gene data was obtained from the ImmPort and InnateDB databases. The weighted gene co-expression network analysis (WGCNA) was used to identify hub immune-related genes. An IRGPI was then constructed using Cox regression methods. Based on the median risk score of IRGPI, patients could be divided into high-risk and low-risk groups. To further investigate the immunologic differences, Gene set variation analysis (GSVA) studies were conducted. In addition, immune cell infiltration and related functional analysis were used to identify the differential immune cell subsets and related functional pathways.

We identified 49 immune-related genes associated with the prognosis of CRC, 17 of which were selected for an IRGPI. The IRGPI model significantly differentiates the survival rates of CRC patients in the different groups. The IRGPI as an independent prognostic factor significantly correlates with clinico-pathological factors such as age and tumor stage. Furthermore, we developed a nomogram to improve the clinical utility of the IRGPI score. Immuno-correlation analysis in different IRGPI groups revealed distinct immune cell infiltration (CD4⁺ T cells resting memory) and associated pathways (macrophages, Type I IFNs responses, iDCs.), providing new insights into the tumor microenvironment. At last, drug sensitivity analysis revealed that the high-risk IRGPI group was sensitive to 11 and resistant to 15 drugs.

Our study established a promising immune-related risk model for predicting survival in CRC patients. This could help to better understand the correlation between immunity and the prognosis of CRC providing a new perspective for personalized treatment of CRC.