1,721,091 research outputs found
A gene expression signature of FOXM1 predicts the prognosis of hepatocellular carcinoma
No full textFOXM1 (Forkhead box M1) is a key regulator of tumorigenesis. Previous studies demonstrated that FOXM1 overexpression was strongly correlated with poor prognosis in various cancers, including hepatocellular carcinoma (HCC). In this study, we examined an association between the gene expression signature of FOXM1 and HCC patient outcome. The co-expressed gene set of FOXM1, which is significantly associated with the prognosis of HCC patients, was identified by analyzing the gene expression profiles of 100 patients with HCC, and this gene set was validated in two independent HCC patient cohorts (n=573). In multivariate analysis, the co-expressed gene set of FOXM1 was the most significant prognostic factor for overall survival in patients with HCC (hazard ratio=1.706, 95% confidence intervals=1.176-2.475, P=0.005). We also analyzed different types of cancer, including pancreatic adenocarcinoma, lung adenocarcinoma, breast carcinoma and bladder urothelial carcinoma, to verify the association between the co-expressed gene set of FOXM1 and patient prognosis, and we found a consistent prognostic significance, regardless of tumor type. Finally, we identified a putative signaling pathway in which miR-34a acts as an upstream regulator of the FOXM1-MYC signaling network; this pathway may be ultimately responsible for the poor prognosis of HCC patients. The prognostic subgroups defined by the gene expression signature of FOXM1 could help predict high-risk patients and may guide selection of the best treatment strategy.
A database of gene expression profiles of Korean cancer genome
No full textBecause there are clear molecular differences entailing different treatment effectiveness between Korean and non-Korean cancer patients, identifying distinct molecular characteristics of Korean cancers is profoundly important. Here, we report a web-based data repository, namely Korean Cancer Genome Database (KCGD), for searching gene signatures associated with Korean cancer patients. Currently, a total of 1,403 cancer genomics data were collected, processed and stored in our repository, an ever-growing database. We incorporated most widely used statistical survival analysis methods including the Cox proportional hazard model, log-rank test and Kaplan-Meier plot to provide instant significance estimation for searched molecules. As an initial repository with the aim of Korean-specific marker detection, KCGD would be a promising web application for users without bioinformatics expertise to identify significant factors associated with cancer in Korean.open
Bioinformatic identification of prognostic signature defined by copy number alteration and expression of CCNE1 in non-muscle invasive bladder cancer
No full textNon-muscle invasive bladder cancer (NMIBC) patients frequently fail to respond to treatment and experience disease progression because of their clinical and biological diversity. In this study, we identify a prognostic molecular signature for predicting the heterogeneity of NMIBC by using an integrative analysis of copy number and gene expression data. We analyzed the copy number and gene expression profiles of 404 patients with bladder cancer obtained from The Cancer Genome Atlas (TCGA) consortium. Of the 14 molecules with significant copy number alterations that were previously reported, 13 were significantly correlated with copy number and expression changes. Prognostic gene sets based on the 13 genes were developed, and their prognostic values were verified in three independent patient cohorts (n=501). Among them, a signature of CCNE1 and its coexpressed genes was significantly associated with disease progression and validated in the independent cohorts. The CCNE1 signature was an independent risk factor based on the result of a multivariate analysis (hazard ratio=6.849, 95% confidence interval=1.613-29.092, P=0.009). Finally, gene network and upstream regulator analyses revealed that NMIBC progression is potentially mediated by CCND1-CCNE1-SP1 pathways. The prognostic molecular signature defined by copy number and expression changes of CCNE1 suggests a novel diagnostic tool for predicting the likelihood of NMIBC progression. ⓒ 2017 KSBMB.
Susceptibility for breast cancer in young patients with short rare minisatellite alleles of BORIS
No full textIn this study, we characterized two blocks of minisatellites in the 5' upstream region of the BORIS gene (BORIS-MS1, -MS2). BORIS-MS2 was found to be polymorphic; therefore, this locus could be useful as a marker for DNA fingerprinting. We assessed the association between BORIS-MS2 and breast cancer by a case-control study with 428 controls and 793 breast cancers cases. Rare alleles in the younger group (age, <40) were associated with a statistically significant increased risk of breast cancer (odds ratio, 4.84; 95% confidence interval, 1.06-22.22; and P = 0.026). A statistically significant association between the short rare alleles and cancer was identified in the younger group (8.02; 1.01-63.83; P = 0.021). Kaplan-Meier estimates showed that poor prognosis was associated with patients who contained the rare alleles. Our data suggest that the short rare alleles of BORIS-MS2 could be used to identify the risk for breast cancer in young patients.open
ADGO: analysis of differentially expressed gene sets using composite GO annotation
No full textMotivation: Genes are typically expressed in modular manners in biological processes. Recent studies reflect such features in analyzing gene expression patterns by directly scoring gene sets. Gene annotations have been used to define the gene sets, which have served to reveal specific biological themes from expression data. However, current annotations have limited analytical power, because they are classified by single categories providing only unary information for the gene sets. Results: Here we propose a method for discovering composite biological hemes from expression data. We intersected two annotated gene sets from different categories of Gene Ontology (GO). We then scored the expression changes of all the single and intersected sets. In this way, we were able to uncover, for example, a gene set with the molecular function F and the cellular component C that showed significant expression change, while the changes in individual gene sets were not significant. We provided an exemplary analysis for HIV-1 immune response. In addition, we tested the method on 20 public datasets where we found many 'filtered' composite terms the number of which reached ∼34% (a strong criterion, 5% significance) of the number of significant unary terms on average. By using composite annotation, we can derive new and improved information about disease and biological processes from expression data.open
A hybrid modeling strategy using Nuclear Overhauser Effect data with contact information
No full textA hybrid modeling strategy using readily assigned Nuclear Overhauser Effect (NOE) data and main chain N-O contact information from homology template proteins is suggested. They are designed to be complementary. The strategy yields structures with reasonable root-mean square distance (RMSD) and NOE violation. When compared to homology-modeled structures, the hybrid-modeled structures are better in terms of RMSD, RMS NOE violation, and protein-like scores, although the number of used restraints is smaller than the homology modeling. The structure itself can be used as a theoretically modeled structure and also as a starting point for further NOE data assignment in structure determination.open
Changes in urinary lithogenic features over time in patients with urolithiasis
No full textObjectives: To assess the changes and sex-specific differences in urinary metabolic risk factors with time. Methods: We performed a retrospective analysis of 619 patients with first-time calcium stone formation (SF) with complete metabolic assessments, who had been diagnosed and treated from 1994 to 2007 at our institution. Patients with SF were categorized into 2 groups according to the date of initial diagnosis: group 1 (1994-1999, n = 353 [57.0%]) and group 2 (2000-2007, n = 266 [43%]). Results: The incidence of obesity was greater in group 2 than in group 1, and this difference was statistically significant among male patients with SF. The urinary pH and total urine volume were lower and the excretion of uric acid was greater in group 2 than in group 1. The incidence of metabolic abnormalities such as low urine volume was more common in group 2 than in group 1. The incidence of hyperuricosuria was increased in male patients with SF in group 2 compared with that in the men in group 1. However, no significant differences were found in the incidence of hyperuricosuria in the female patients with SF between groups 1 and 2. Conclusions: The pattern of urinary lithogenic factors in Korean patients with SF has changed with time. Hyperuricosuria has become more prevalent in recent years. We found a high prevalence of hyperuricosuria in men, which might have been due to the increased incidence of obesity in this subgroup.open
Lipocalin-2 negatively modulates the epithelial-to-mesenchymal transition in hepatocellular carcinoma through the epidermal growth factor (TGF-beta1)/Lcn2/Twist1 pathway
No full textLipocalin-2 (Lcn2) is preferentially expressed in hepatocellular carcinoma (HCC). However, the functional role of Lcn2 in HCC progression is still poorly understood, particularly with respect to its involvement in invasion and metastasis. The purpose of this study was to investigate whether Lcn2 is associated with the epithelial-mesenchymal transition (EMT) in HCC and to elucidate the underlying signaling pathway(s). Lcn2 was preferentially expressed in well-differentiated HCC versus liver cirrhosis tissues, and its expression was positively correlated with the stage of HCC. The characteristics of EMT were reversed by adenoviral transduction of Lcn2 into SH-J1 cells, including the down-regulation of N-cadherin, vimentin, alpha-smooth muscle actin, and fibronectin, and the concomitant up-regulation of CK8, CK18, and desmoplakin I/II. Knockdown of Lcn2 by short hairpin RNA (shRNA) in HKK-2 cells expressing high levels of Lcn2 was associated with EMT. Epidermal growth factor (EGF) or transforming growth factor beta1 (TGF-β1) treatment resulted in down-regulation of Lcn2, accompanied by an increase in Twist1 expression and EMT in HCC cells. Stable Lcn2 expression in SH-J1 cells reduced Twist1 expression, inhibited cell proliferation and invasion in vitro, and suppressed tumor growth and metastasis in a mouse model. Furthermore, EGF or TGF-β1 treatment barely changed EMT marker expression in SH-J1 cells ectopically expressing Lcn2. Ectopic expression of Twist1 induced EMT marker expression even in cells expressing Lcn2, indicating that Lcn2 functions downstream of growth factors and upstream of Twist1. Conclusion: Together, our findings indicate that Lcn2 can negatively modulate the EMT in HCC cells through an EGF (or TGF-β1)/Lcn2/Twist1 pathway. Thus, Lcn2 may be a candidate metastasis suppressor and a potential therapeutic target in HCC.open
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