Development of an exosome-related and immune microenvironment prognostic signature in colon adenocarcinoma

Abstract

Background: The correlation between exosomes and the tumor immune microenvironment has been proved to affect tumorigenesis and progression of colon adenocarcinoma (COAD). However, it remained unclear whether exosomes had an impact on the prognostic indications of COAD patients.Methods: Expression of exosome-related genes (ERGs) and clinical data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The ERGs associated with prognosis were identified and exosome-related prognostic signature was constructed. Patients in two risk groups were classified according to the risk score calculation formula: Risk score = 1.0132 * CCKBR + 0.2416 * HOXC6 + 0.7618 * POU4F1. The expression of three ERGs was investigated by qRT-PCR. After that, we developed a nomogram predicting the likelihood of survival and verified its predictive efficiency. The differences of tumor immune microenvironment, immune cell infiltration, immune checkpoint and sensitivity to drugs in two risk groups were analyzed.Results: A prognostic signature was established based on the three ERGs (CCKBR, HOXC6, and POU4F1) and patients with different risk group were distinguished. Survival analysis revealed the negative associated of risk score and prognosis, ROC curve analyses showed the accuracy of this signature. Three ERGs expression was investigated by qRT-PCR in three colorectal cancer cell lines. Moreover, risk score was positively correlated with tumor mutational burden (TMB), immune activities, microsatellite instability level, the expression of immune checkpoint genes. Meanwhile, the expression level of three ERGs and the risk score were markedly related with the sensitive response to chemotherapy.Conclusion: The novel signature composed of three ERGs with precise predictive capabilities can be used to predict prognosis and provide a promising therapeutic target for improving the efficacy of immunotherapy.

HOXC6: A promising biomarker linked to an immunoevasive microenvironment in colorectal cancer based on TCGA analysis and cohort validation

“…Some studies have suggested that HOXC6 is associated with immune dysfunction. In colon adenocarcinoma, a predictive hallmark according to the presence of CCKBR, HOXC6 , and POU4F1 was discovered to be actively related to immune activity, microsatellite instability, gene expression of immune checkpoints, and poor sensitivity to chemotherapy [ 49 ]. This study was based on the TCGA and Gene Expression Omnibus (GEO) databases for bioinformatics analyses.…”

Identification and verification of a prognostic signature based on a miRNA–mRNA interaction pattern in colon adenocarcinoma

“…In the present study, POU4F1, which paired with miR-150-5p, was a neuro transcription factor that was closely related to AML1/ETO gene fusion in acute myeloid leukemia ( Dunne et al, 2010 ). It might affect the prognosis of patients with COAD through exosomes and the tumor immune microenvironment ( Cui et al, 2022 ).…”

Regulatory role of exosomes in colorectal cancer progression and potential as biomarkers

“…It has been shown that exosomes mediate crosstalk between immune cells and MSI/MSS CRC, and participate in the regulation of CRC immune status and function in the TME 149 . Cui et al 150 identified three exosome-related genes (ERGs) as key prognostic genes in CRC patients through bioinformatics analysis and confirmed that these ERGs were highly expressed in multiple CRC cells. Cui et al 150 calculated risk scores for CRC patients based on the coefficients of these ERGs and divided patients into high- and low-risk groups.…”

“…Cui et al 150 identified three exosome-related genes (ERGs) as key prognostic genes in CRC patients through bioinformatics analysis and confirmed that these ERGs were highly expressed in multiple CRC cells. Cui et al 150 calculated risk scores for CRC patients based on the coefficients of these ERGs and divided patients into high- and low-risk groups. Further analysis revealed that the levels of resting CD4 memory T cells, resting dendritic cells, and activated dendritic cells were higher in patients with low-risk scores, while the level of activated NK cells was higher in patients with a high-risk score.…”