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.

Background Vasculogenic mimicry (VM) is a recently identified pattern of blood supply to tumor tissue. It has long been considered a functional element in the metastasis and prognosis of malignant tumors. Both Rho GTPase-activating protein 25 (ARHGAP25) and Ras homolog family member A (RhoA) are effective predictors of tumor metastasis. In this study, we examined the expression levels of ARHGAP25 and RhoA and the structure of VM in non-small cell lung cancer (NSCLC). At the same time, we used cytology-related experiments to explore the effect of ARHGAP25 on the migration ability of tumor cells. Furthermore, we analyzed the interaction between the three factors and their association with clinicopathological characteristics and the five-year survival time in patients using statistical tools. Methods A total of 130 well-preserved NSCLC and associated paracancerous tumor-free tissues were obtained. Cell colony formation, wound healing, and cytoskeleton staining assays were used to analyze the effect of ARHGAP25 on the proliferation and migration ability of NSCLC cells. Immunohistochemical staining was used to determine the positivity rates of ARHGAP25, RhoA, and VM. Statistical software was used to examine the relationships between the three factors and clinical case characteristics, overall survival, and disease-free survival. Results Cell colony formation, wound healing, and cytoskeleton staining assays confirmed that ARHGAP25 expression affects the proliferation and migratory abilities of NSCLC cells. ARHGAP25 positivity rates in NSCLC and paracancerous tumor-free tissues were 48.5% and 63.1%, respectively, whereas RhoA positivity rates were 62.3% and 18.5%, respectively. ARHGAP25 had a negative relationship with RhoA and VM, whereas RhoA and VM had a positive relationship (P < 0.05). ARHGAP25, RhoA, and VM affected the prognosis of patients with NSCLC (P < 0.05) according to Kaplan–Meier of survival time and Cox regression analyses. Furthermore, lowering ARHGAP25 expression increased NSCLC cell proliferation and migration. Conclusions ARHGAP25 and RhoA expression is associated with VM and may be of potential value in predicting tumor metastasis, prognosis, and targeted therapy.

Type IIA topoisomerase (TOP2A) is significantly associated with malignant tumor development, invasion, treatment and its prognosis, and has been shown to be a therapeutic target against cancer. In contrast, the role of TOP2A in the immunotherapy of non-small cell lung cancer as well as in Vasculogenic mimicry (VM) formation and its potential mechanisms are unclear. The aim of this study was to investigate the role of TOP2A in proliferation, skeleton regulation, motility and VM production in non-small cell lung cancer and its mechanisms by using bioinformatics tools and molecular biology experiments. Subgroup analysis showed that the low-risk group had a better prognosis, while the high-risk group was positively correlated with high tumor mutational load, M1-type macrophage infiltration, immune checkpoint molecule expression, and immunotherapy efficacy. As confirmed by further clinical specimens, the presence of TOP2A and VM was significantly and positively correlated with poor prognosis. Our study established a model based on significant co-expression of TOP2A genes, which significantly correlated with mutational load and immunotherapy outcomes in patients with non-small cell lung cancer. Further mechanistic exploration suggests that TOP2A plays an important role in immunotherapy and VM formation in NSCLC through upregulation of Wnt3a and PD-L1 expression.

Background: Type IIA topoisomerase (TOP2A) is significantly associated with malignant tumor development, invasion, treatment and its prognosis, and has been shown to be a therapeutic target against cancer. In contrast, the role of TOP2A in the immunotherapy of non-small cell lung cancer as well as in VM formation and its potential mechanisms are unclear. Methods: Based on the 82 significantly co-expressed genes of TOP2A screened, consensus molecular typing was performed by the NMF algorithm, and the effect of immunotherapy was further evaluated in two groups of patients with high and low risk. The expression of TOP2A and VM in non-small cell lung cancer tissues was assessed by immunohistochemistry. Western Blot, colony formation assay, CCK8 assay, cell cycle and apoptosis assay, tube-forming assay and cytoskeleton staining were used to verify the role of TOP2A in proliferation, skeleton regulation, motility and VM generation in non-small cell lung cancer and its mechanism. Results: Patients with lung adenocarcinoma were distinguished into high- and low-risk subgroups based on significant co-expression of TOP2A genes. Subgroup analysis showed that patients in the low-risk group had a better prognosis, while higher risk was associated with higher tumor mutational load, M1-type macrophage and immune checkpoint molecule expression. The Tumor Immune Dysfunction and Rejection (TIDE) and Tumor Immunome Atlas (TCIA) databases also showed significant differences in the outcome of immunotherapy in patients with different types of lung adenocarcinoma. As verified by further clinical specimens, the presence of both TOP2A and VM were significantly and positively correlated with poor prognosis. TOP2A may ultimately affect immunotherapy and VM formation in non-small cell lung cancer through its involvement in regulating the expression of Wnt3a and PD-L1. Conclusion: A model based on significantly co-expressed genes of TOP2A was significantly correlated with mutational load and immunotherapeutic effects in patients with non-small cell lung cancer. TOP2A plays an important role in immunotherapy and VM formation in non-small cell lung cancer through upregulation of Wnt3a and PD-L1 expression.