Dataset Information

Upregulation of BUB1B, CCNB1, CDC7, CDC20, and MCM3 in Tumor Tissues Predicted Worse Overall Survival and Disease-Free Survival in Hepatocellular Carcinoma Patients.

ABSTRACT: Objective:To evaluate the association between upregulated differentially expressed genes (DEGs) and the outcomes of patients with hepatocellular carcinoma (HCC). Methods:Using Gene Expression Omnibus (GEO) datasets including GSE45436, GSE55092, GSE60502, GSE84402, and GSE17548, we detected upregulated DEGs in tumors. KEGG, GO, and Reactome enrichment analysis of the DEGs was conducted to clarify their function. The impact of the upregulated DEGs on patients' survival was analyzed based on TCGA profile. Results:161 shared upregulated DEGs were identified among GSE45436, GSE55092, GSE60502, and GSE84402 profiles. Cell cycle was the shared pathway/biological process in the gene sets investigation among databases of KEGG, GO, and Reactome. After being validated in GSE17548, 13 genes including BUB1B, CCNA2, CCNB1, CCNE2, CDC20, CDC6, CDC7, CDK1, CDK4, CDKN2A, CHEK1, MAD2L1, and MCM3 in cell cycle pathway were shared in the three databases for enrichment. The expression of BUB1B, CCNB1, CDC7, CDC20, and MCM3 was upregulated in HCC tissues when compared with adjacent normal tissues in 6.67%, 7.5%, 8.06%, 5.56%, and 9.72% of HCC patients, respectively. Overexpression of BUB1B, CCNB1, CDC7, CDC20, and MCM3 in HCC tissues accounted for poorer overall survival (OS) and disease-free survival (DFS) in HCC patients (all log rank P < 0.05). BUB1B, CCNB1, CDC7, CDC20, and MCM3 were all overexpressed in HCC patients with neoplasm histologic grade G3-4 compared to those with G1-2 (all P < 0.05). BUB1B, CCNB1, and CDC20 were significantly upregulated in HCC patients with vascular invasion (all P < 0.05). Additionally, levels of BUB1B, CCNB1, CDC7, and CDC20 were significantly higher in HCC patients deceased, recurred, or progressed (all P < 0.05). Conclusion:Correlated with advanced histologic grade and/or vascular invasion, upregulation of BUB1B, CCNB1, CDC7, CDC20, and MCM3 in HCC tissues predicted worse OS and DFS in HCC patients. These genes could be novel therapeutic targets for HCC treatment.

SUBMITTER: Zhuang L

PROVIDER: S-EPMC6186344 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Upregulation of BUB1B, CCNB1, CDC7, CDC20, and MCM3 in Tumor Tissues Predicted Worse Overall Survival and Disease-Free Survival in Hepatocellular Carcinoma Patients.

Zhuang Liping L Yang Zongguo Z Meng Zhiqiang Z

BioMed research international 20180930

<h4>Objective</h4>To evaluate the association between upregulated differentially expressed genes (DEGs) and the outcomes of patients with hepatocellular carcinoma (HCC).<h4>Methods</h4>Using Gene Expression Omnibus (GEO) datasets including GSE45436, GSE55092, GSE60502, GSE84402, and GSE17548, we detected upregulated DEGs in tumors. KEGG, GO, and Reactome enrichment analysis of the DEGs was conducted to clarify their function. The impact of the upregulated DEGs on patients' survival was analyzed ...[more]

PMID: 30363964

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Project description:Background Pancreatic ductal adenocarcinoma (PDAC) displays a typical mucin expression pattern which is characterized by MUC1 positive, MUC2 negative, and MUC5AC positive. More and more evidences show that mucins are involved in the development of pancreatic diseases. However, the relationship between mucin expression and prognosis of PDAC patients has been controversial in the past decades; therefore, we aim to figure out the association of mucin expression with survival in PDAC patients who underwent radical resection. Methods We performed immunohistochemistry (IHC) to detect the expression of MUC1, MUC2, and MUC5AC in resected PDAC specimens from Shanghai Cancer Center, Fudan University (FUSCC, n = 427) and obtained the corresponding clinical statistical data for retrospective study. Kaplan-Meier methods and Mantel-Cox tests were used to compare the survival curves, and the Cox regression model was employed for multivariate analyses to determine the independent risk factors. Survival analysis was also performed in the Queensland Centre for Medical Genomics (QCMG, n = 70) PDAC cohort to verify the conclusion. Results Both the FUSCC cohort and the QCMG cohort demonstrated that MUC1 absence was significantly correlated with worse overall survival (OS). The presence of MUC2 showed marginal significance in predicting shorter OS of PDAC patients, while MUC5AC had no prognostic value. In the FUSCC cohort, MUC1 absence was associated with increased proportion of stage III PDAC (p = 0.011), and MUC1 absence and MUC2 presence were associated with tumour perineural aggression (p = 0.011 and p = 0.030, respectively). Multivariable adjusted hazard ratios (HRs) for mortality of MUC1 and MUC2 were 0.492 (95% CI: 0.274-0.883, p = 0.017) and 1.596 (95% CI: 1.061-2.401, p = 0.025), respectively. Conclusions MUC1 absence or MUC2 presence is independently associated with poor OS among patients with resectable PDAC. MUC5AC absence tended to be associated with short-term death.

Project description:Pancreatic ductal adenocarcinoma (PDAC) remains a major cause of cancer-associated mortality, with poor patient outcome. The present study aimed to identify key candidate genes and investigate the potential molecular mechanisms associated with the progression of PDAC. The GSE46234 dataset was downloaded from the Gene Expression Omnibus database, in order to identify the upregulated differentially expressed genes (DEGs) in PDAC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the biological functions and pathways of the upregulated DEGs, and a protein-protein interaction (PPI) network was subsequently constructed to screen the hub genes. Subsequently, survival analyses of the hub genes were undertaken in patients with PDAC, using The Cancer Genome Atlas dataset. Reverse transcription-quantitative (RT-q)PCR analysis was performed to assess the mRNA expression levels of the hub genes associated with the prognosis of patients with PDAC. In the present study, 65 upregulated DEGs were identified. GO analysis suggested that the DEGs were enriched in response to hypoxia, calcium ion and negative regulation of catecholamine. KEGG analysis demonstrated that the DEGs were enriched in gastric acid secretion, the ECM-receptor interaction and the cGMP-PKG signaling pathway. Among the 18 hub genes determined by module screening of the PPI network, upregulation of three key genes, abnormal spindle-like microcephaly-associated protein (ASPM), mitotic checkpoint serine/threonine-protein kinase BUB1 ? (BUB1B) and protein spindly (SPDL1), was significantly associated with worse overall survival and disease-free survival time in patients with PDAC. Furthermore, ASPM, BUB1B and SPDL1 were demonstrated to be associated with advanced tumor stage, and their upregulation in PDAC tumor tissues was validated using RT-qPCR analysis. Taken together, the results of the present study demonstrate that ASPM, BUB1B and SPDL1 may have the potential to function as prognostic markers and therapeutic targets for PDAC.

Project description:AimLung metastases are a negative prognostic factor in Ewing sarcoma, however, the incidence and significance of sub-centimetre pulmonary nodules at diagnosis is unclear. The aims of this study were to (1): determine the incidence of indeterminate pulmonary nodules (IPNs) in patients diagnosed with Ewing sarcoma (2); establish the impact of IPNs on overall and metastasis-free survival and (3) identify patient, oncological and radiological factors that correlate with poorer prognosis in patients that present with IPNs on their staging chest CT.Materials & methodsBetween 2008 and 2016, 173 patients with a first presentation of Ewing sarcoma of bone were retrospectively identified from an institutional database. Staging and follow-up chest CTs for all patients with IPN were reviewed by a senior radiologist. Clinical and radiologic course were examined to determine overall- and metastasis-free survival for IPN patients and to identify demographic, oncological or nodule-specific features that predict which IPN represent true lung metastases.ResultsFollowing radiologic re-review, IPN were found in 8.7% of patients. Overall survival for IPN patients was comparable to those with a normal staging chest CT (2-year overall survival of 73.3% [95% CI 43.6-89] and 89.4% [95% CI 81.6-94], respectively; p = 0.34) and was significantly better than for patients with clear metastases (46.0% [95% CI 31.9-59]; p < 0.0001). Similarly, there was no difference in metastasis-free survival between 'No Metastases' and 'IPN' patients (p = 0.16). Lung metastases developed in 40% of IPN patients at a median 9.6 months. Reduction of nodule size on neoadjuvant chemotherapy was associated with worse overall survival in IPN patients (p = 0.0084).ConclusionIPN are not uncommon in patients diagnosed with Ewing sarcoma. In this study, we were unable to detect a difference in overall- or metastasis-free survival between patients with IPN at diagnosis and patients with normal staging chest CTs.

Project description:IntroductionHepatocellular carcinoma (HCC) is the most common primary liver cancer with a low 5-year survival rate. The heterogeneity of HCC makes monotherapy unlikely. The development of diagnostic programs and new treatments targeting common genetic events in the carcinogenic process are providing further insights into the management of HCC. The aim of this study was firstly to validate key genes that are involved in promoting HCC development and as biomarkers for early diagnosis and, secondly, to define their links with antitumor immunity including inhibitory checkpoints.MethodsMultiple databases including Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, UALCAN, and Oncomine were used for target gene screening and establishment of a co-expression network. Clinical data and RNAseq of 367 HCC patients were downloaded from the Cancer Genome Atlas (TCGA) database. The diagnostic and prognostic value of screened genes were tested by receiver operating characteristic (ROC) curve and correlation analysis. The links with the key genes in HCC and antitumor immunity were defined using both blood and liver tissue collected prospectively from HCC patients in our center.ResultsUpregulation of CCNB1, CDC20, and CENPF was commonly observed in HCC and are involved in the p53 signal pathway. The hepatic mRNA expression levels of these three genes were strongly associated with patients' prognosis and expressed high value of area under the ROC curve (AUC). Further analysis revealed that these three genes were positively correlated with the gene expression levels of IFN-γ, TNF-α, and IL-17 in peripheral blood. In addition, the expression of CENPF showed positive correlation with the percentage of CD8pos T cells and negative correlation with the percentage of CD4pos T cells in the peripheral blood. In the HCC microenvironment, the transcript levels of these three genes and inhibitory checkpoint molecules including PD-1, CTLA-4, and TIM-3 were positively correlated.ConclusionThe upregulation of CCNB1, CDC20, and CENPF genes was a common event in hepatocarcinogenesis. Expression levels of CCNB1, CDC20, and CENPF showed potential for early diagnosis and prediction of prognosis in HCC patients. There is a close association between three genes and Th1/Th17 cytokines as well as the count of CD4pos and CD8pos T cells. The positive correlation between the three genes and inhibitory checkpoint genes, PD-1, CTLA-4, and TIM-3, indicates that these genes are linked with weakened antitumor immunity in HCC. Our findings may provide further insights into developing novel therapies for HCC.

Dataset Information

Upregulation of BUB1B, CCNB1, CDC7, CDC20, and MCM3 in Tumor Tissues Predicted Worse Overall Survival and Disease-Free Survival in Hepatocellular Carcinoma Patients.

Publications

Upregulation of BUB1B, CCNB1, CDC7, CDC20, and MCM3 in Tumor Tissues Predicted Worse Overall Survival and Disease-Free Survival in Hepatocellular Carcinoma Patients.

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