Abstract
With highly homologous epidermal growth factor (EGF)-like (EGFL) domains, the members of the EGFL family play crucial roles in growth, invasion, and metastasis of tumors and are closely associated with the apoptosis of tumor cells and tumor angiogenesis. Furthermore, their contribution to immunoreaction and tumor microenvironment is highly known. In this study, a comprehensive analysis of EGFL6, −7, and −8 was performed on the basis of their expression profiles and their relationship with the rate of patient survival. Through a pan-cancer study, their effects were correlated with immune subtypes, tumor microenvironment, and drug resistance. Using The Cancer Genome Atlas pan-cancer data, expression profiles of EGFL6, −7, and −8, and their association with the patient survival rate and tumor microenvironment were analyzed in 33 types of cancers. The expression of the EGFL family was different in different cancer types, revealing the heterogeneity among cancers. The results showed that the expression of EGFL8 was lower than EGFL6 and EGFL7 among all cancer types, wherein EGFL7 had the highest expression. The univariate Cox proportional hazard regression model showed that EGFL6 and EGFL7 were the risk factors to predict poor prognosis of cancers. Survival analysis was then used to verify the relationship between gene expression and patient survival. Furthermore, EGFL6, EGFL7, and EGFL8 genes revealed a clear association with immune infiltrate subtypes; they were also related to the infiltration level of stromal cells and immune cells with different degrees. Moreover, they were negatively correlated with the characteristics of cancer stem cells measured by DNAs and RNAs. In addition, EGFL6, −7, and −8 were more likely to contribute to the resistance of cancer cells. Our systematic analysis of EGFL gene expression and their correlation with immune infiltration, tumor microenvironment, and prognosis of cancer patients emphasized the necessity of studying each EGFL member as a separate entity within each particular type of cancer. Simultaneously, EGFL6, −7, and −8 signals were verified as promising targets for cancer therapies, although further laboratory validation is still required.
Highlights
Epidermal growth factor (EGF)-like (EGFL) domain gene family is named so because the protein structure of its members contains single or multiple EGFL domains
Were CHOL, glioblastoma multiforme (GBM), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), prostate adenocarcinoma (PRAD), and thyroid carcinoma (THCA), whereas those having a high level of EGFL6 expression were bladder urothelial carcinoma (BLCA), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and uterine corpus endometrial carcinoma (UCEC)
Several studies have shown that EGFL6, EGFL7, and EGFL8 play a crucial role in the process of tumor growth, invasion, and distant metastasis
Summary
Epidermal growth factor (EGF)-like (EGFL) domain gene family is named so because the protein structure of its members contains single or multiple EGFL domains. The members of the EGFL family have symbolic homology with EGF and can be attributed to EGF-related proteins because they have highly homologous EGFL domains. They have common functional characteristics (Soncin et al, 2003; Parker et al, 2004; Schmidt et al, 2007). The most studied EGFL family members were EGFL6, EGFL7, and EGFL8 They have a similar structure and functional characteristics and have a unique structure and function. On the basis of investigations and experiments, we discussed the relationship among EGFL6, −7, and −8 and tumor development and prognosis
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