Abstract
Purpose: The aims of the present study were to explore immune-related genes (IRGs) in stage IV colorectal cancer (CRC) and construct a prognostic risk score model to predict patient overall survival (OS), providing a reference for individualized clinical treatment.Methods: High-throughput RNA-sequencing, phenotype, and survival data from patients with stage IV CRC were downloaded from TCGA. Candidate genes were identified by screening for differentially expressed IRGs (DE-IRGs). Univariate Cox regression, LASSO, and multivariate Cox regression analyses were used to determine the final variables for construction of the prognostic risk score model. GSE17536 from the GEO database was used as an external validation dataset to evaluate the predictive power of the model.Results: A total of 770 candidate DE-IRGs were obtained, and a prognostic risk score model was constructed by variable screening using the following 12 genes: FGFR4, LGR6, TRBV12-3, NUDT6, MET, PDIA2, ORM1, IGKV3D-20, THRB, WNT5A, FGF18, and CCR8. In the external validation set, the survival prediction C-index was 0.685, and the AUC values were 0.583, 0.731, and 0.837 for 1-, 2- and 3-year OS, respectively. Univariate and multivariate Cox regression analyses demonstrated that the risk score model was an independent prognostic factor for patients with stage IV CRC. High- and low-risk patient groups had significant differences in the expression of checkpoint coding genes (ICGs).Conclusion: The prognostic risk score model for stage IV CRC developed in the present study based on immune-related genes has acceptable predictive power, and is closely related to the expression of ICGs.
Highlights
Colorectal cancer (CRC) ranks third for both morbidity and mortality among cancers worldwide [1]
Development of prognostic risk models can further improve treatment strategies for stratified management; most existing prognostic risk models were constructed based on data from patients with CRC overall or those with postoperative stage II CRC [5,6,7,8]
Genes with |log2 fold changes (FC)| ≥ 1 and adjusted P
Summary
Colorectal cancer (CRC) ranks third for both morbidity and mortality among cancers worldwide [1]. Most CRC patients (approximately 50–60%) have stage IV disease at initial diagnosis [2,3,4]. Stage IV CRC has a better prognosis, relative to other metastatic gastrointestinal malignancies [1]. At present, both the European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) have established specific clinical practice guidelines for patients with stage IV CRC and recommended the stratified management of such patients with different disease characteristics, typifying current connotation of ‘precision medicine’. CRC is a heterogeneous disease, and prognosis varies significantly among patients. It is necessary to establish a prognostic prediction model for individual with stage IV CRC
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