Background: VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 are important proteins involved in the induction and development of a new blood vessel network through which the tumor is properly nourished and oxygenated. Objective: The aim of the study was to evaluate changes in VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 expression in endometrial cancer depending on its grade and to determine the VEGFR-1 to VEGFR-2 concentration ratio. Methods: The study group consisted of 45 patients diagnosed with endometrial cancer (G1, 17; G2, 15; G3, 13). The control group included 15 patients. VEGF-A, VEGF-B, VEGF-R1, VEGFR-2 expression was assessed using the immunohistochemical method. Statistical analysis was carried out using the Statistica 12 PL program (StatSoft, Cracow, Poland). It included the one-way ANOVA and Tukey's post-hoc test (pG2>G1>C; VEGF-B: G2> G3> G1>C. A lower concentration of VEGFR-1 than VEGFR-2 was found regardless of the cancer grade. Conclusion: VEGF-A, VEGF-B, VEGF-R1, VEGFR-2 are key proteins involved in tumor angiogenesis. The analysis of the entire panel of proteins participating in a given process is an important element of modern diagnostics. The concentration ratio of VEGFR-1 to VEGFR-2 appears to be a determining factor in the patients' survival prognosis.
18 October 2019 in Current Pharmaceutical Biotechnology
Background: Vascular endothelial growth factor (VEGF)-C, -D, and VEGF receptor-3 are proteins characterized as crucial for tumor lymphangiogenesis. It is accompanied by angiogenesis during wound healing, but also in the neoplastic process. The research studies have shown that the lymphatic system plays a key role in the progression of carcinogenesis.Objective: The aim of this study was to evaluate changes in the expression of VEGF-C, VEGF-D and VEGFR-3 in different grades of endometrial cancer (G1-G3).Methods: The study included 45 patients diagnosed with endometrial cancer (G1=17; G2=15; G3=13) and 15 patients without neoplastic changes. The expression of VEGF-C, VEGF-D, and VEGFR-3 was assessed using microarray technique and immunohistochemistry. Statistical analysis was performed using the one-way ANOVA and Tukey's post-hoc test.Results: Statistically significant changes in the expression at the transcriptome level were found only in the case of VEGF-C (G1 vs. C, fold change - FC = -1.15; G2 vs. C, FC = -2.33; G3 vs. C, FC = - 1.68). However, VEGF-D and VEGFR-3 were expressed at the protein level. Analysis of VEGF-D expression showed that the optical density of the reaction product in G1 reached 101.7, while the values in G2 and G3 were 142.7 and 184.4, respectively. For VEGF-R3, the optical density of the reaction product reached the following levels: 72 in control, 118.77 in G1, 145.8 in G2, and 170.9 in G3.Conclusion: : An increase in VEGF-D and VEGFR-3 levels may indicate that VEGF-D-dependent processes are intensified along with the dedifferentiation of tumor cells. The lack of VEGF-C expression in endometrial cancer samples may suggest that this tumor is characterized by a different mechanism of metastasis than EMT. Our study emphasizes that when analyzing the metastatic potential of cancer, the expression of more than one factor should be taken into account.
This study aimed to assess the expression profile of messenger RNA (mRNA) and microRNA (miRNA) related to the dopaminergic system in five types of breast cancer in Polish women. Patients with five breast cancer subtypes were included in the study: luminal A (n = 130), luminal B (n = 196, including HER2−, n = 100; HER2+, n = 96), HER2+ (n = 36), and TNBC (n = 43); they underwent surgery, during which tumor tissue was removed along with a margin of healthy tissue (control material). The molecular analysis included a microarray profile of mRNAs and miRNAs associated with the dopaminergic system, a real-time polymerase chain reaction preceded by reverse transcription for selected genes, and determinations of their concentration using enzyme-linked immunosorbent assay (ELISA). The conducted statistical analysis showed that five mRNAs statistically significantly differentiated breast cancer sections regardless of subtype compared to control samples; these were dopamine receptor 2 (DRD2), dopamine receptor 3 (DRD3), dopamine receptor 25 (DRD5), transforming growth factor beta 2 (TGF-β-2), and caveolin 2 (CAV2). The predicted analysis showed that hsa-miR-141-3p can regulate the expression of DRD2 and TGF-β-2, whereas hsa-miR-4441 is potentially engaged in the expression regulation of DRD3 and DRD5. In addition, the expression pattern of DRD5 mRNA can also be regulated by has-miR-16-5p. The overexpression of DRD2 and DRD3, with concomitant silencing of DRD5 expression, confirms the presence of dopaminergic abnormalities in breast cancer patients. Moreover, these abnormalities may be the result of miR-141-3P, miR-16-5p, and miR-4441 activity, regulating proliferation or metastasis.
BACKGROUND:SEMA3B is known as an inhibitor of angiogenesis and cell proliferation. During carcinogenesis, the loss of SEMA3B function is observed, which results in the progression of neoplastic changes. The aim of this study was to evaluate the expre...
The aim of this study was to identify miRNAs that could potentially influence the activity of SMAD proteins involved in TGFβ signal transduction in five types of breast cancer in Polish women. Patients with five breast cancer subtypes were included in the study: luminal A (n = 130), luminal B HER2− (n = 100), luminal B HER2+ (n = 96), non-luminal HER2+ (n = 36), and TNBC (n = 43). During surgery, tumor tissue was removed along with a margin of healthy tissue (control). Molecular analysis included determination of the expression of genes related to SMAD protein signal transduction using mRNA microarrays and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Protein expression was determined using an enzyme-linked immunosorbent assay (ELISA). The miRNA profiling was performed using miRNA microarrays and the miRDB database. SMAD3 and SMAD5 were overexpressed in all types of breast cancer, which could be related to the reduced expression of miR-145, and the findings for SMAD4 and miR-155 were similar. Additionally, the level of SMAD7 was reduced, which may be due to the low activity of miR-15b and miR21b. This study determined the gene expression profiles involved in SMAD protein signal transduction across five different types of breast cancer and identified the miRNAs potentially regulating their activity. Overexpression of SMAD3, SMAD4, and SMAD5 suggests excessive activation of the TGFβ pathway, potentially promoting tumor growth and development. Concurrently, a significant reduction in SMAD7 expression removes inhibitory control in the TGFβ pathway, a phenomenon that is particularly evident in more aggressive breast cancer types.
The purpose of this study was to evaluate the relationship between human papillomavirus (HPV16/18), Epstein–Barr virus (EBV), and human cytomegalovirus (HCMV) infections and the occurrence of ovarian cancer in 48 women, of whom 36 underwent surgery and chemotherapy (group A), 12 in whom surgery was sufficient (group B), and 60 with endometroid endometrial cancer stage G1-G3 (group C), compared to patients in whom the uterus and its appendages were removed for nononcological reasons (control group). The detection of HPV, EBV, and HCMV in tumor tissue and normal tissue was performed using the real-time polymerase chain reaction (RT-PCR) technique. A statistically significantly higher risk of endometrial cancer was noted in patients infected only with HCMV (OR > 1; p < 0.05). In contrast, a significantly higher risk of ovarian cancer in group A was associated with HPV16, HPV18, and EBV (OR > 1; p < 0.05); a significantly higher risk of ovarian cancer in group B was associated with HPV18 and HMCV (OR > 1; p < 0.05). The obtained results suggest that HCMV infection is associated with the development of a stage of ovarian cancer when treatment can be completed with surgery alone. Meanwhile, EBV appears to be responsible for the development of ovarian cancer in more advanced stages.