Cell division cycle proteinising prognostic biomarker of breast cancer.

Cell division cycle protein (CDC20) has been observed to be expressed higher in various kinds of human cancers and was associated with poor prognosis. However, studies on role of CDC20 in breast cancer are seldom reported till now, most of which are not systematic and conclusive. The present study was performed to analyze the expression pattern, potential function, and distinct prognostic effect of CDC20 in breast cancer using several online databases including Oncomine, bc-GenExMiner, PrognoScan, and UCSC Xena. To verify the results from databases, we compared the mRNA CDC20 expression in breast cancer tissues and adjacent normal tissues of patients by real-time PCR. We found that CDC20 was expressed higher in different types of breast cancer, comparing with normal tissues. Moreover, the patients with a more advanced stage of breast cancer tended to express higher level CDC20. CDC20 was expressed higher in breast cancer tissues than normal tissues from patients in our hospital, consistent with the results from databases. Estrogen receptor (ER) and progesterone receptor (PR) status were negatively correlated with CDC20 level. Conversely, Scarff-Bloom-Richardson (SBR) grade, Nottingham prognostic index (NPI), epidermal growth factor receptor-2 (HER-2) status, basal-like status, and triple-negative status were positively related to CDC20 expression in breast cancer patients with respect to normal individuals. Higher CDC20 expression correlated with worse survival. Finally, a positive correlation between CDC20 and Targeting protein for Xenopus kinesin-like protein 2 (TPX2) expression was revealed. CDC20 could be considered as a potential predictive indicator for prognosis of breast cancer with co-expressed TPX2 gene.

Elevated mRNA Levels of AURKA, CDC20 and TPX2 are associated with poor prognosis of smoking related lung adenocarcinoma using bioinformatics analysis.

Background and aim: Adenocarcinoma is a very common pathological subtype for lung cancer. We aimed to identify the gene signature associated with the prognosis of smoking related lung adenocarcinoma using bioinformatics analysis. Methods: A total of five gene expression profiles (GSE31210, GSE32863, GSE40791, GSE43458 and GSE75037) have been identified from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using GEO2R software and functional and pathway enrichment analysis. Furthermore, the overall survival (OS) and recurrence-free survival (RFS) have been validated using an independent cohort from the Cancer Genome Atlas (TCGA) database. Results: We identified a total of 58 DEGs which mainly enriched in ECM-receptor interaction, platelet activation and PPAR signaling pathway. Then according to the enrichment analysis results, we selected three genes (AURKA, CDC20 and TPX2) for their roles in regulating tumor cell cycle and cell division. The results showed that the hazard ratio (HR) of the mRNA expression of AURKA for OS was 1.588 with (1.127-2.237) 95% confidence interval (CI) (P=0.009). The mRNA levels of CDC20 (HR 1.530, 95% CI 1.086-2.115, P=0.016) and TPX2 (HR 1.777, 95%CI 1.262-2.503, P=0.001) were also significantly associated with the OS. Expression of these three genes were not associated with RFS, suggesting that there might be many factors affect RFS. Conclusion: The mRNA signature of AURKA, CDC20 and TPX2 were potential biomarkers for predicting poor prognosis of smoking related lung adenocarcinoma.

Identification of genes involved in the four stages of colorectal cancer: Gene expression profiling.

BACKGROUND: Colorectal cancer (CRC) is a common cancer with high morbidity and mortality. However, its molecular mechanism is not clear, nor the genes related to CRC stages. METHODS: Gene expression data in CRC and healthy colorectal tissues were obtained from gene expression omnibus. Limma package was used to identify the differentially expressed genes (DEGs) between control and CRC (stage I, II, III, and IV), obtaining 4 DEG sets. VennPlex was utilized to find all DEGs and intersection DEGs. Functional interactions between all DEGs and protein-protein interactions (PPIs) between intersection DEGs were analyzed using ReactomeFIViz and STRING, respectively, and networks were visualized. Known CRC-related genes were down-loaded from Comparative Toxicogenomics Database and mapped to PPI network. RESULTS: Totally, 851, 760, 729, and 878 DEGs were found between control and CRC stage I, II, III, and IV, respectively. Taken together, 1235 DEGs were found, as well as 128 up-regulated intersection DEGs, 365 down-regulated intersection DEGs, and 0 contra-regulated DEG. A functional interaction network of all DEGs and a PPI network of intersection DEGs were constructed, in which CDC20, PTTG1, and MAD2L1 interacted with BUB1B; UGT2B17 interacted with ADH1B; MCM7 interacted with MCM2. BUB1B, ADH1B, and MCM2 were known CRC-related genes. Gradually upregulated expressions of CDC20, PTTG1, MAD2L1, UGT2B17, and MCM7 in stage I, II, III, and IV CRC were confirmed by using quantitative PCR. Besides, up-regulated intersection DEGs enriched in pathways about Cell cycle, DNA replication, and p53 signaling. CONCLUSION: CDC20, PTTG1, MAD2L1, UGT2B17, and MCM7 might be CRC stage-related genes.

Proteins of the mitotic checkpoint and spindle are related to chromosomal instability and unfavourable prognosis in patients with myelodysplastic syndrome.

AIMS: To study the immunoexpression of proteins related to the mitotic checkpoint (cell division cycle 20 (CDC20), mitotic arrest deficient 2 (MAD2)) and the mitotic spindle (Aurora-B) in patients with myelodysplastic syndrome (MDS). METHODS: Protein expression was analysed in bone marrow tissue samples from 40 patients with MDS using immunohistochemistry. Prognostic markers (transfusion dependency, depth of cytopenias, chromosomal abnormalities and survival) were also studied. RESULTS: Higher MAD2 expression was observed among patients with platelets <50×10(9)/L than among patients with platelets ≥50×10(9)/L (42.6±22.8% vs 22.7±19.1%, respectively). Higher CDC20 expression was identified among patients with three dysplasias compared with patients who presented with one or two dysplasias (33.9±24.1% vs 10.5±5.7% vs 12.8±7.8%, respectively), among patients who exhibited a complex versus non-complex karyotype (50.0±30.2% vs 18.4±14%, respectively) and among patients with platelets <50×10(9)/L vs platelets ≥50×10(9)/L (38.2±26.2% vs 16.1±12.4%, respectively). Higher Aurora-B expression was found in patients with an abnormal versus normal karyotype (21.2±13.2% vs 7.5±5.0%, respectively). High expression of MAD2 and CDC20 (≥50%) was associated with severe thrombocytopenia. We also found statistically significant differences in the overall survival rate when comparing different degrees of CDC20, MAD2 and Aurora-B protein expression. CONCLUSIONS: To the best of our knowledge, this is the first report to demonstrate that these proteins are associated with chromosomal abnormalities and poor prognosis in patients with MDS.

Expression characteristics of CDC20 in gastric cancer and its correlation with poor prognosis.

The cell division cycle 20 homolog (CDC20) expression is increased in diverse human cancers and plays a vital role in tumorigenesis and progression. However, the clinical significance of CDC20 expression in gastric cancer (GC) remains largely unknown. The aim of this study was to investigate the clinicopathologic features and prognostic significance of CDC20 in GC. The CDC20 mRNA expression was measured by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) was used to detect the expression of CDC20 protein in 131 clinicopathologically characterized GC cases. The relationship between CDC20 expression and clinicopathological features was analyzed by appropriate statistics. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between CDC20 expression and prognosis of GC patients. The relative mRNA expression of CDC20 were significantly higher in GC tumor tissues than in the corresponding noncancerous tissues (P<0.001). Simultaneously, CDC20 protein expression was positively correlated with tumor size (P=0.02), histological grade (P=0.037), lymph node involvement (P=0.009), and TNM stage (P=0.015). Furthermore, Kaplan-Meier analysis indicated that patients with high CDC20 expression had poor overall survival (P<0.001). Multivariate analysis showed that high CDC20 expression was an independent predictor of overall survival. In conclusion, our data indicated that CDC20 upregulation was associated with aggressive progression and poor prognosis in GC. CDC20 was identified for the first time as an independent marker for predicting the clinical outcome of GC patients.

High CDC20 expression is associated with poor prognosis in oral squamous cell carcinoma.

OBJECTIVES: Human Cell Division Cycle 20 (CDC20) homolog is a crucial target of the spindle assembly checkpoint. It is an activator of the Anaphase-Promoting Complex/Cyclosome (APC/C) which promotes anaphase onset and mitotic exit through the ubiquitination of securin and cyclin B1. Overexpression of CDC20 was previously reported in oral squamous cell carcinoma (OSCC). Here, we propose to explore the clinicopathological significance of CDC20 overexpression and its potential use as a prognostic marker in OSCC. METHODS: Using tissue microarray technology, we analyzed CDC20 expression in 65 primary OSCC tissues by immunohistochemistry. Statistical analysis was performed to evaluate the clinicopathological and prognostic significance of CDC20 expression in OSCC. RESULTS: Of the 65 cases of patients with OSCC studied, 37 (56.9%) showed high CDC20 protein expression. No clinicopathological features were correlated with CDC20 expression. Importantly, in univariable analysis, OSCC patients with higher CDC20 protein expression showed significantly shorter cancer-specific survival rate (P = 0.018). Multivariable analysis identified high CDC20 expression as an independent prognostic factor (P = 0.032). CONCLUSION: High CDC20 expression is associated with poor prognosis in OSCC and may be used to identify high-risk OSCC patients and may serve as a therapeutic target.