Development of an Immune Infiltration-Related Eight-Gene Prognostic Signature in Colorectal Cancer Microenvironment
Beilei Wu1, Lijun Tao2, Daqing Yang3
1Medical Examination Center, Wenzhou Central Hospital, The Dingli Clinical College of Wenzhou Medical University, Wenzhou, 325000 Zhejiang, China.
Objective:
Stromal cells and immune cells have important clinical significance in the microenvironment of colorectal cancer (CRC). This study is aimed at developing a CRC gene signature on the basis of stromal and immune scores.
Methods:
A cohort of CRC patients (n = 433) were adopted from The Cancer Genome Atlas (TCGA) database. Stromal/immune scores were calculated by the ESTIMATE algorithm. Correlation between prognosis/clinical characteristics and stromal/immune scores was assessed. Differentially expressed stromal and immune genes were identified. Their potential functions were annotated by functional enrichment analysis. Cox regression analysis was used to develop an eight-gene risk score model. Its predictive efficacies for 3 years, 5 years, overall survival (OS), and progression-free survival interval (PFI) were evaluated using time-dependent receiver operating characteristic (ROC) curves. The correlation between the risk score and the infiltering levels of six immune cells was analyzed using TIMER. The risk score was validated using an independent dataset.
Results:
Immune score was in a significant association with prognosis and clinical characteristics of CRC. 736 upregulated and two downregulated stromal and immune genes were identified, which were mainly enriched into immune-related biological processes and pathways. An-eight gene prognostic risk score model was conducted, consisting of CCL22, CD36, CPA3, CPT1C, KCNE4, NFATC1, RASGRP2, and SLC2A3. High risk score indicated a poor prognosis of patients. The area under the ROC curves (AUC) s of the model for 3 years, 5 years, OS, and PFI were 0.71, 0.70, 0.73, and 0.66, respectively. Thus, the model possessed well performance for prediction of patients' prognosis, which was confirmed by an external dataset. Moreover, the risk score was significantly correlated with immune cell infiltration.
Conclusion:
Our study conducted an immune-related prognostic risk score model, which could provide novel targets for immunotherapy of CRC.
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