Significance of ZEB2 in the immune microenvironment of colon cancer

Abstract

Background: ZEB2 is a protein-coding gene that is differentially expressed in tumors and can regulate the growth of tumor cells. This study investigated the specific regulatory mechanism of ZEB2 in COAD, a common cancer with high rates of morbidity and mortality.Methods: Multi-omics panoramic display of expression and function of ZEB2 in colon cancer. R software was used to study the expression of ZEB2 in 33 types of cancer. Furthermore, RT-PCR was used to detect the expression of ZEB2 in colon cancers and para-cancer tissues, as well as in colon cancer cells and normal cells. The ssGSEA was then used to explore the relationship between ZEB2 and immune cells, with UALCAN, EWAS and MEXPRESS applied to explore the methylation of ZEB2. The relationship between immunomodulators and chemokines (or receptors) based on expression data, copy number data, methylation data, and mutation data of ZEB2 was investigated using TISIDB. Finally, a protein interaction network of ZEB2 was constructed, and GO and KEGG analyses were performed on the differentially expressed genes.Results: ZEB2 is downregulated in most cancers, including COAD. The infiltration of the immune cells NK CD56 and Th17 cells was negatively correlated with ZEB2 expression, while the other 22 cells were positively correlated with ZEB2 expression. The DNA methylation of ZEB2 and the methylation of the ZEB2 protein on the EWAS website increased significantly. Analysis of the methylation levels and ZEB2 expression revealed that only the DNA methylation level and the expression of ZEB2 were significantly negatively correlated. The tumor-infiltrating lymphocytes positively correlated with the expression of ZEB2 but negatively correlated with the methylation of ZEB2. The same trend was observed for immunomodulators, chemokines, and receptors. The network showed that the protein performed certain biological functions, thereby affecting disease symptoms.Conclusion: These findings provide evidence that ZEB2-based therapy may represent a powerful treatment strategy for COAD.

Endogenous retroviruses mediate transcriptional rewiring in response to oncogenic signaling in colorectal cancer

“…S42). This supports our results from the single-cell and bulk patient analyses and suggests that expression of these zinc fingers is protective ( 48 , 49 ). We speculate that one of the ways in which loss of these zinc fingers contributes to cancer progression is by derepressing LTR10 enhancers and enabling the pathological activity of LTR10 target genes.…”

ZEB family is a prognostic biomarker and correlates with anoikis and immune infiltration in kidney renal clear cell carcinoma

“…ZEB1 has been discovered to promote the generation of immune-suppressive cells and chemokines within the tumor microenvironment (TME), leading to the formation of an immunosuppressive barrier around infiltrating cancer cells by activating immune checkpoints, leading to an immunosuppressive microenvironment [ 58 , 59 ]. In the context of colon cancer, ZEB2 has been recognized as a crucial participant in the immune microenvironment [ 60 ]. Through GSEA enrichment analyses, the current investigation has revealed the participation of ZEB1 and ZEB2 in various pathways, specifically the complement cascade.…”

Prognostic value of SLC4A4 and its correlation with the microsatellite instability in colorectal cancer

“…Recently, the relationship between microsatellite instability and the occurrence and development of tumors has become a topic of interest in the study of tumor markers, characteristics, and prognosis. Although there have been many in-depth studies on potential biomarkers of tumors, few biomarkers can be used in combination with MSI to evaluate patient prognosis (25)(26)(27)(28). MSI is a feature of many disorders, most of which are neoplastic, with Lynch syndrome being the most well-known non-neoplastic disorder.…”