Exploring Immune-Related Prognostic Signatures in the Tumor Microenvironment of Colon Cancer

Abstract

Background: Colon cancer is a common malignant tumor with poor prognosis. The aim of this study is to explore the immune-related prognostic signatures and the tumor immune microenvironment of colon cancer.Methods: The mRNA expression data of TCGA-COAD from the UCSC Xena platform and the list of immune-related genes (IRGs) from the ImmPort database were used to identify immune-related differentially expressed genes (DEGs). Then, we constructed an immune-related risk score prognostic model and validated its predictive performance in the test dataset, the whole dataset, and two independent GEO datasets. In addition, we explored the differences in tumor-infiltrating immune cell types, tumor mutation burden (TMB), microsatellite status, and expression levels of immune checkpoints and their ligands between the high-risk and low-risk score groups. Moreover, the potential value of the identified immune-related signature with respect to immunotherapy was investigated based on an immunotherapeutic cohort (Imvigor210) treated with an anti-PD-L1 agent.Results: Seven immune-related DEGs were identified as prognostic signatures. The areas under the curves (AUCs) of the constructed risk score model for overall survival (OS) were calculated (training dataset: 0.780 at 3 years, 0.801 at 4 years, and 0.766 at 5 years; test dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years; and the whole dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years). In the high-risk score group of the whole dataset, patients had worse OS, higher TMN stages, advanced pathological stages, and a higher TP53 mutation rate (p < 0.05). In addition, a high level of resting NK cells or M0 macrophages, and high TMB were significantly related to poor OS (p < 0.05). Also, we observed that high-risk score patients had a high expression level of PD-L1, PD-1, and CTLA-4 (p < 0.05). The patients with high-risk scores demonstrated worse prognosis than those with low-risk scores in multiple datasets (GSE39582: p = 0.0023; GSE17536: p = 0.0008; immunotherapeutic cohort without platinum treatment: p = 0.0014; immunotherapeutic cohort with platinum treatment: p = 0.0027).Conclusion: We developed a robust immune-related prognostic signature that performed great in multiple cohorts and explored the characteristics of the tumor immune microenvironment of colon cancer patients, which may give suggestions for the prognosis and immunotherapy in the future.

Development and validation of a necroptosis-related gene prognostic score to predict prognosis and efficiency of immunotherapy in gastric cancer

“…In China, about 95% of GC patients have the characteristics of microsatellite stability (MSS) (61). Patients with GC in the MSI-H group had a higher survival rate and significantly more benefit from immunotherapy in contrast to the MSS/MSI-L group (62,63). Consistently, according to our research, the high-NRGPS group of GC patients had a larger percentage of MSS and a lower percentage of MSI-H.…”

Characterization of Platelet Function-Related Gene Predicting Survival and Immunotherapy Efficacy in Gastric Cancer

“…Patients with GC in the MSI-H group had higher survival rates than patients in the MSS or low-MSI groups ( Zhang et al, 2022 ). In patients with colon cancer, it was found that patients in the MSI-H group benefited significantly more from immunotherapy than patients in the MSS or MSI-L groups ( Cao et al, 2022 ). Our study found that patients with GC in the high-PRFGPS subgroup had a higher proportion of MSS and a lower proportion of MSI-H.…”

Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies

“…[287][288][289][290][291] A positive correlation between EMT and immune checkpoint proteins was identified in multiple cancer types, including lung, breast, colorectum, oral, and esophageal cancers, 289,292-297 and a higher expression of these checkpoint molecules indicates worse prognosis in a broad range of cancers. [298][299][300] The functional relationship between immune checkpoint proteins and therapy evasion suggests that a combination treatment with immune checkpoint blockade (ICB) could be promising in developing a new approach against TCP.…”