Abstract
BackgroundAlthough immunotherapy for colon cancer has made promising progress, only a few patients currently benefit from it. A recent study revealed that infiltrating immune cells are highly relevant to tumor prognosis and influence the expression of immune-related genes. However, the characterization of immune cell infiltration (ICI) has not yet been comprehensively analyzed and quantified in colon adenocarcinoma (COAD).MethodsThe multiomic data of COAD samples were downloaded from TCGA. ESTIMATE algorithm, ssGSEA method and CIBERSORT analysis were conducted to estimate the subpopulations of infiltrating immune cells. COAD subtypes based on ICI pattern were identified by consensus clustering then principal-component analysis was performed to obtain ICI scores to quantify the ICI patterns in individual tumors. Kaplan–Meier analysis was employed to validate prognostic value. Gene set enrichment analysis (GSEA) was applied for functional annotation. Finally, the mutation data was analyzed by employing “maftools” package.ResultsThree bioinformatics algorithms were used to evaluate the ICI patterns from 538 patients with COAD. Two ICI subtypes were determined using consensus clustering, and the ICI score was constructed by performing principal component analysis. Our findings showed that a higher ICI score often indicated a more advanced tumor and worse prognosis. The high-ICI score subgroup had a higher stromal score and more M0 macrophages but fewer plasma cells and decreased CD8 T cell infiltration. In addition, patients with high ICI scores had significantly higher expression levels of HAVCR2 and PCDC1LG2. Real-time polymerase chain reaction (PCR) was conducted to determine the prognostic significances of ICI-related genes.ConclusionsIn conclusion, ICI score may be considered as an original and useful indicator for independent prognostic prediction and individual immune-related therapy.
Highlights
Colon adenocarcinoma (COAD), a type of colorectal cancer (CRC), is the third most common cancer and the third leading cause of cancer-related deaths in both menXu et al Cancer Cell Int (2021) 21:344At present, colon cancer is primarily treated with surgery, radiotherapy, and chemotherapy
Based on the immune cell infiltration (ICI) patterns of 538 CRC samples from the TCGA-colon adenocarcinoma (COAD) and GSE29623 datasets, we clustered the CRC patients into different subgroups using the R software package “ConsensusClusterPlus.” According to the similarity shown in the ICI profiles, the consensus matrix had the best clustering stability when k = 2, and the cumulative distribution function value, which is considered as an indicator of outstanding clustering, tended to increase (Additional file 2: Figure S1A–F)
There was no significant difference in overall survival (OS) time as shown by the Kaplan–Meier plotter (Fig. 1B; P = 0.878), we observed that the OS of ICI cluster A was higher than that of ICI cluster B after 5 years
Summary
Colon adenocarcinoma (COAD), a type of colorectal cancer (CRC), is the third most common cancer and the third leading cause of cancer-related deaths in both menXu et al Cancer Cell Int (2021) 21:344At present, colon cancer is primarily treated with surgery, radiotherapy, and chemotherapy. Immunotherapy, especially immune checkpoint blockade (ICB), has emerged as an original method that exerts surprising therapeutic effects in various types of cancers, such as melanoma as well as renal and lung carcinoma [2]. Patients with mismatch repair deficiency (dMMR) and DNA polymerase epsilon mutations are usually accompanied by a higher degree of T cell infiltration and response to immune checkpoint inhibitors, which indicates a better clinical prognosis [3]. Only a limited number of patients with a high mutation burden can benefit from immune checkpoint inhibitors. Immunotherapy for colon cancer has made promising progress, only a few patients currently benefit from it. The characterization of immune cell infiltration (ICI) has not yet been comprehensively analyzed and quantified in colon adenocarcinoma (COAD)
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