Mengting Li1, Haizhou Wang1, Wenjie Li1, Yanan Peng1, Fei Xu1, Jian Shang1, Shouquan Dong1, Lupin Bu1, Hao Wang1, Wanhui Wei1, Qian Hu1, Lan Liu2, Qiu Zhao3. 1. Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China. 2. Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China. Electronic address: lliugi@whu.edu.cn. 3. Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China. Electronic address: qiuzhao@whu.edu.cn.
Abstract
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Although the significant efficacy of immunotherapy has been shown, only limited CRC patients benefit from it. Therefore, we aimed to establish a prognostic signature based on immune-related genes (IRGs) to predict overall survival (OS) and the potential response to immunotherapy in CRC patients. METHODS: Gene expression profiles and clinical information of CRC patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The prognostic signature composed of IRGs was established using univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) regression analysis. CIBERSORT was used to estimate the immune cell infiltration. RESULTS: A total of 24 survival-related IRGs were identified from 247 differentially expressed IRGs. Then, 16 IRGs were selected to establish the prognostic signature that stratified the patients into the high-risk and low-risk groups with statistically different survival outcomes. The AUCs of the time-dependent ROC curves indicated that the signature had a strong predictive accuracy in internal and external validation sets. Multivariate cox regression analysis suggested that the signature could also act as an independent prognostic factor for OS. The low-risk group had a higher proportion of immune cell infiltration than the high-risk group, such as CD4 memory resting T cells, activated dendritic cells, and resting dendritic cells. In addition, patients in the high-risk group exhibited higher tumor mutation burden and BRAF mutation. CONCLUSION: We developed an immune-related prognostic signature to predict the OS and immune status in CRC patients. We believed that our signature is conducive to better stratification and more precise immunotherapy for CRC patients.
BACKGROUND:Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Although the significant efficacy of immunotherapy has been shown, only limited CRCpatients benefit from it. Therefore, we aimed to establish a prognostic signature based on immune-related genes (IRGs) to predict overall survival (OS) and the potential response to immunotherapy in CRCpatients. METHODS: Gene expression profiles and clinical information of CRCpatients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The prognostic signature composed of IRGs was established using univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) regression analysis. CIBERSORT was used to estimate the immune cell infiltration. RESULTS: A total of 24 survival-related IRGs were identified from 247 differentially expressed IRGs. Then, 16 IRGs were selected to establish the prognostic signature that stratified the patients into the high-risk and low-risk groups with statistically different survival outcomes. The AUCs of the time-dependent ROC curves indicated that the signature had a strong predictive accuracy in internal and external validation sets. Multivariate cox regression analysis suggested that the signature could also act as an independent prognostic factor for OS. The low-risk group had a higher proportion of immune cell infiltration than the high-risk group, such as CD4 memory resting T cells, activated dendritic cells, and resting dendritic cells. In addition, patients in the high-risk group exhibited higher tumor mutation burden and BRAF mutation. CONCLUSION: We developed an immune-related prognostic signature to predict the OS and immune status in CRCpatients. We believed that our signature is conducive to better stratification and more precise immunotherapy for CRCpatients.