The Relationship Between UBE2C and AGGF1 Overexpression and Tumor Angiogenesis in Non-Small Cell Lung Cancer

Abstract

Background Tumor infiltration and metastasis are the leading causes of death for patients with tumors. Angiogenesis is a prerequisite for tumor growth and metastasis. Angiogenic factor with G patch and FHA domains 1 (AGGF1) is an angiogenic factor, whereas ubiquitin-conjugating enzyme E2C (UBE2C) functions in protein ubiquitination. Microvessel density (MVD) is the most common indicator of tumor microvessels, and vasculogenic mimicry (VM) facilitates blood supply to tumors. This study explored UBE2C and AGGF1 expression in non-small cell lung cancer (NSCLC) and their relationship with angiogenesis and prognosis to identify biological factors that might predict NSCLC infiltration, metastasis, and prognosis. Methods The specimens and clinical pathological data of patients with NSCLC confirmed by pathology after surgical resection between January 2013 and December 2015 were collected. UBE2C and AGGF1 expression, as well as microvessel formation and VM in NSCLC, was observed using immunohistochemistry. The relationships between UBE2C, AGGF1, MVD, VM, and clinical pathological parameters and their relationships with overall survival (OS) and disease-free survival (DFS) were analyzed. Results UBE2C and AGGF1 levels in NSCLC tissues were significantly higher than those in corresponding normal tissues (57.1% vs 15.6 and 59.7% vs 25.3%, respectively; P < 0.05). UBE2C, AGGF1, MVD, and VM were positively correlated with each other ( P < 0.05) and were all related to tumor size, lymph node metastasis, and tumor-node-metastasis stage ( P < 0.05). Kaplan–Meier analysis showed that patient OS and DFS in the UBE2C, AGGF1, VM-positive, and high-MVD groups were reduced (all P < 0.001). Univariate and multivariate analyses showed that UBE2C, AGGF1, VM, and MVD were independent risk factors for NSCLC prognosis. Conclusion UBE2C and AGGF1 overexpression is associated with angiogenesis and poor prognosis and may be important for predicting NSCLC invasion, metastasis, and prognosis.

Aberrant expression of UBE2C in endometrial cancer and its correlation to epithelial mesenchymal transition

“…[8,21] The normal of this function is associated with completion of cell cycle and signal transduction. [9,22] In our study, the result demonstrated that UBE2C expression is significantly higher in EC tissues than that in the control tissues. We found that UBE2C expression is positively rated to tumor stages, LNM, and FIGO stages.…”

“…Overexpression of UBE2C can promote tumorigenesis and be associated with unfavorable overall survival (OS) and progression-free survival of cancer patients. [5,[7][8][9] The wingless MMTV integration site (WNT) multigene family encodes secreted extracellular signaling proteins that regulate cell polarity, motility, and pattern during embryogenesis and tissue homeostasis. The WNT family contains19 highly conserved glycoproteins.…”

UBE2C: A pan‐cancer diagnostic and prognostic biomarker revealed through bioinformatics analysis

“…16,17 Consistent with our finding, previous studies reported that the UBE2C mRNA expression was higher in various cancers including hepatocellular, 28 esophageal squamous cell, 29 adrenocortical carcinoma, 30 gastric, 31 breast, 32 and lung cancers. 33 UBE2C is a part of the ubiquitin proteasome system, having a key function in the regulation of cell cycle progression via the degradation of mitotic cyclins to control the M phase to the G1 phase transition and also engaging in mitotic spindle checkpoint control. 34,35 Upregulated UBE2C expression disturbs the ubiquitination system required for protein degradation, leading to aberrant cell proliferation as a common feature of malignant transformation in a wide range of malignancies.…”

“…[36][37][38] Taken higher UBE2C gene expression appeared to be a useful prognostic indicator associated with poor prognosis and higher frequencies of tumor metastasis and progression. [28][29][30][31][32][33] Furthermore, we indicated that the expression level of UBE2C has altered in different pathological stages that positively correlated with cancer stage and the results showed higher expression of UBE2C involved in cancer progression and invasion. 16,30,39,40 As well, the result showed that significant high protein expression levels of UBE2C protein in 20 different cancer type increase.…”

LATPS, a novel prognostic signature based on tumor microenvironment of lung adenocarcinoma to better predict survival and immunotherapy response

“…Reportedly, these four genes correlated with patient survival. Overexpression of UBE2C was reported as an independent risk factor associated with dismal outcomes in patients with lung cancer ( 36 , 37 ). Reportedly, KRT6A is associated with cell proliferation and invasion, which drives cancer progression by upregulating glucose-6-phosphate dehydrogenase (G6PD) through MYC signaling pathway ( 38 ).…”