Abstract
RNF183, a member of the E3 ubiquitin ligase, has been shown to involve in carcinogenesis and proposed as one of the biomarkers in Uterine Corpus Endometrial Carcinoma (UCEC). However, no research focused on the role of RNF183 in UCEC. We analyzed the expression and immune infiltration of RNF183 in UCEC. TIMER, UALCAN, and GEPIA were used to analyze the gene expression of RNF183. We emplored Kaplan-Meier Plotter to examine the overall survival and progression-free survival of RNF183, and applied GeneMANIA to identify RNF183-related functional networks. LinkedOmics was helpful to identify the differential gene expression of RNF183, and to further analyze gene ontology and the genome pathways in the Kyoto Protocol. Finally, we used TIMER to investigate the immune infiltration of RNF183 in UCEC. Otherwise, we partly verified the results of bioinformatics analysis that RNF183 controlled ERα expression in ERα-positive Ishikawa cells dependent on its RING finger domain. We also found that ERα increased the stability of RNF183 through the post-translational mechanism. Together, patients with a high level of RNF183 harbor favorable overall and progression-free survival. High expression of RNF183 was associated with a low stage, endometrioid, and TP53 Non-Mutant status in endometrial cancer. The RNF183 expression was greater at higher expression and the tumor stage was greater at the lower level. On the side of immunization, high level of RNF183 in UCEC is negatively related to tumor purity, infiltrating levels of CD4 + T cells, neutrophils, and dendritic cells. Besides, the expression of RNF183 in UCEC is significantly correlated with the expression of several immune cell markers, including B cell, M1 macrophage marker, M2 Macrophage, Dendritic cell, Th1 markers, Th2 markers, Treg markers, and T cell exhaustion markers, indicating its role in regulating tumor immunity. These results suggested that RNF183 may be considered as a novel prognostic factor in endometrial cancer and an early diagnostic indicator for patients with UCEC.
Highlights
Uterine Corpus Endometrial Carcinoma (UCEC) is the fourth most common gynecological malignancy in developed countries (Kandoth et al, 2013), and the incidence has been raised rapidly in China, increasing 63,400 new cases a year (Chen et al, 2016)
From the the majority of human cancers (TIMER) database of the Diff Exp module across all the cancer genome atlas (TCGA) tumors, our studying showed that a high proportion of RNF183 exists in the majority of human cancer tissues (Figure 1A)
RNF183 was shown to be elevated in cancerous tissues compared to normal endometrium (Figure 1B), which was accordant with statistics documented in Gene Expression Profiling Interactive Analysis (GEPIA) (Figure 1C)
Summary
Uterine Corpus Endometrial Carcinoma (UCEC) is the fourth most common gynecological malignancy in developed countries (Kandoth et al, 2013), and the incidence has been raised rapidly in China, increasing 63,400 new cases a year (Chen et al, 2016). Type I endometrial cancer is often endometrioid and well-differentiated, presumably owing to greater exposure to a long history of unopposed estrogen or other risk factors inducing hyperestrogenism such as obesity. Endometrial cancer is one of the few human malignant tumors for which mortality is increasing (Berg et al, 2017), which underlines the urgency to develop more effective methods for the early diagnosis and treatment of this disease. RING finger ubiquitin ligases are involved in the process of essential cellular functions, such as maintaining the integrity of genomic, cell cycle, cell signal, and DNA repair. RING finger E3s are involved both in the promotion and the suppression of cancers. Accumulation functional and controlled pathway data from RING finger E3s are helpful for developing new targeted therapy
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