ABSTRACT
BACKGROUND: Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it's role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. METHODS: In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. RESULTS: As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p < 0.05). Meanwhile, high CDC6 expression was associated with poor overall survival (OS) in glioma patients, especially in different clinical subgroups. Furthermore, a univariate Cox analysis showed that high CDC6 expression was correlated with poor OS in glioma patients. Functional enrichment analysis indicated that CDC6 was mainly involved in pathways related to DNA transcription and cytokine activity, and Gene Set Enrichment Analysis (GSEA) revealed that MAPK pathway, P53 pathway and NF-κB pathway in cancer were differentially enriched in glioma patients with high CDC6 expression. Single-sample gene set enrichment analysis (ssGSEA) showed CDC6 expression in glioma was positively correlated with Th2 cells, Macrophages and Eosinophils, and negative correlations with plasmacytoid dendritic cells, CD8 T cells and NK CD56bright cells, suggesting its role in regulating tumor immunity. Finally, CCK8 assay, flow cytometry and transwell assays showed that silencing CDC6 could significantly inhibit proliferation, migration, invasion, and promoted apoptosis of U87 cells and U251 cells (p < 0.05). CONCLUSION: In conclusion, high CDC6 expression may serve as a promising biomarker for prognosis and correlated with immune infiltrates, presenting to be a potential immune therapy target in glioma.
Subject(s)
Brain Neoplasms , Glioma , Biomarkers , Brain Neoplasms/metabolism , Cell Cycle Proteins/genetics , Glioma/pathology , Humans , NF-kappa B , Nuclear Proteins/genetics , PrognosisABSTRACT
PURPOSE: To identify new effective prognostic indicators for patients with nasopharyngeal carcinoma (NPC). METHODS: The immunohistochemical staining method was used to detect cyclooxygenase-2 (COX-2) protein in tumor tissues of 100 patients before and after chemoradiation. All the patients had stage III poorly differentiated NPC. RESULTS: The positive expression of COX-2 was decreased before and after chemotherapy. The expression levels of COX-2 in patients before treatment was associated with T stage (p<0.05). The changes in the positive expression of COX-2 following treatment was also associated with T stage (p<0.05). The clinical response rate (CR+PR) exhibited significant differences (p<0.05) in patients with negative, weakly positive, partially positive, and strongly positive COX-2 expression before treatment. The clinical response rate (CR+PR) exhibited significant differences (p<0.05) compared with the patients who were negative or weakly positive. The COX-2 positive expression level of patients with NPC before treatment was closely associated with the survival time and survival rate of the patients (p<0.05). The changes of COX-2 positive expression were associated with the survival time and survival rate (p<0.05) in patients with NPC following treatment. T stage, COX-2 expression before treatment and changes in COX-2 expression after treatment were independent factors affecting NPC prognosis (p<0.05). CONCLUSION: Changes in COX-2 expression levels before and after treatment may be a useful indicator for assessing the prognosis of NPC after chemoradiotherapy.
Subject(s)
Cyclooxygenase 2/metabolism , Nasopharyngeal Carcinoma/enzymology , Nasopharyngeal Carcinoma/therapy , Chemoradiotherapy , Cyclooxygenase 2/biosynthesis , Female , Humans , Immunohistochemistry , Male , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/radiotherapy , Neoplasm Staging , Prognosis , Survival AnalysisABSTRACT
OBJECTIVE: To detect and analyze the therapeutic effects of X-ray knife for treatment of choroidal melanoma with the fixation of the eyeball. METHODS: The average size of the tumors in 16 eyes of 16 cases was 11.8 mm x 10.0 mm x 4.5 mm. The eyeballs were fixed with four rectus retractable sutures under local anesthesia (no use of retrobulbar injection). The superior and inferior rectus sutures penetrated the upper and lower lids at the middle part of fornixes, and the four sutures were anchored at the positions: above the eyebrow, inferior orbital rim, root of nose and lateral orbital rim respectively and deep to the fascia. A stereotactic linear accelerator, Vrianc 2100 C, was used for the radiosurgery, with an average marginal dose 23.4 Gy. The mean follow-up time was 18.5 months. RESULTS: The tumors in 7 cases (43.8%) shrinked notably during 6 - 12 months after therapy. In the postoperative 1 - 2 years, the tumors in 11 eyes (68.8%) were decreased in size, among them, in 4 eyes only a flat scar remained and in 3 eyes the shrinkage was not significant. Enucleation was performed in 3 patients because of a little increase in size. The total local control rate was 81.3%. There were no marked side effects except small hemorrhages in or under the retina. Fixations of all eyeballs were very stable, and the orientation of radiotherapy was accurate. CONCLUSIONS: The therapeutic effects of choroidal melanoma with X-ray knife are quite good, and no significant complications are found. There is a higher rate of local control. The fixation of eyeball with four rectus sutures penetrating eyelids is very stable and reliable.