Abstract

BackgroundColorectal cancer (CRC) is a common malignant tumor of the digestive tract with a high mortality rate. Growing evidence demonstrates that immune-related genes play a prominent role in the occurrence and development of CRC. The aim of this study was to investigate the prognostic value of immune-related genes in CRC.MethodsGene expression profiles and clinical data of 568 CRC and 44 non-tumorous tissues were obtained from The Cancer Genome Atlas (TCGA) database. First, we performed a differentially expressed gene (DEG) analysis and univariate Cox regression analysis to determine the DEGs associated with overall survival. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed for prognostic immune-related genes. Then, a multivariate Cox regression analysis was performed to establish the immune prognostic model and identify the independent prognostic factors of CRC. Next, in vitro experiments were done to further validate the model. Finally, we analyzed the correlation among immune-related genes, clinical traits, and immune cell infiltration.ResultsIn total, 3,702 DEGs were obtained, and 338 prognostic immune-related genes were identified. Among them, 45 genes were significantly correlated with the prognosis of CRC patients. A TF-mediated network was set up to explore its internal mechanism. GO and KEGG analyses further illustrated that these genes were enriched in immune-and inflammatory-related pathways. Then, a prognostic prediction model composed of eight immune-related genes (SLC10A2, UTS2, FGF2, UCN, IL1RL2, ESM1, ADIPOQ, and VIP) was constructed. The AUC of the ROC curve for 1, 3, 5, and 10 years overall survival (OS) was 0.751, 0.707, 0.680, and 0.729, respectively. The survival analysis suggested that the OS of the high-risk group was significantly poorer than that of the low-risk group. Meanwhile, in vitro assays revealed that ESM1 and SLC10A2 exert opposing roles in colon cancer cell proliferation, validating the accuracy of the model. The correlation analysis indicated that immune cell infiltration was positively related to the model.ConclusionThis study screened prognosis-related immune genes and developed a prognostic prediction model of CRC. These findings may help provide potential novel prognostic biomarkers and therapeutic targets for CRC. At the same time, the understanding of the CRC immune microenvironment status was deepened.

Highlights

  • Colorectal cancer (CRC) is known as the third most common cancer globally and has the second-highest leading number of cancer-related deaths worldwide (Keum and Giovannucci, 2019)

  • All 338 immune-related differentially expressed genes (DEGs) were analyzed by Gene ontology (GO) and The Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses

  • The results indicated that the most enriched biological processes (BP) were leukocyte migration, cell chemotaxis, and leukocyte chemotaxis

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Summary

Introduction

Colorectal cancer (CRC) is known as the third most common cancer globally and has the second-highest leading number of cancer-related deaths worldwide (Keum and Giovannucci, 2019). Because the early symptoms of CRC are not obvious, most patients are overlooked (Or et al, 2017). They are often diagnosed in intermediate or late stages and have poor prognoses with the symptoms of hematochezia, abdominal pain, and altered bowel habits, as well as emaciation (Dekker et al, 2019). Despite recent progress in testing and treatments, the overall prognosis for patients with CRC remains poor because biomarkers for early detection and prognosis prediction are lacking (Keum and Giovannucci, 2019). The aim of this study was to investigate the prognostic value of immune-related genes in CRC

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