Bleckmann, Annalen

[["dc.bibliographiccitation.artnumber","135"],["dc.bibliographiccitation.journal","Frontiers in Oncology"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Bayerlová, Michaela"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Wolff, Alexander"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Bleckmann, Annalen"],["dc.date.accessioned","2019-07-09T11:43:27Z"],["dc.date.available","2019-07-09T11:43:27Z"],["dc.date.issued","2017"],["dc.description.abstract","Breast cancer is a heterogeneous disease and has been classified into five molecular subtypes based on gene expression profiles. Signaling processes linked to different breast cancer molecular subtypes and different clinical outcomes are still poorly understood. Aberrant regulation of Wnt signaling has been implicated in breast cancer progression. In particular Ror1/2 receptors and several other members of the non-canonical Wnt signaling pathway were associated with aggressive breast cancer behavior. However, Wnt signals are mediated via multiple complex pathways, and it is clinically important to determine which particular Wnt cascades, including their domains and targets, are deregulated in poor prognosis breast cancer. To investigate activation and outcome of the Ror2-dependent non-canonical Wnt signaling pathway, we overexpressed the Ror2 receptor in MCF-7 and MDA-MB231 breast cancer cells, stimulated the cells with its ligand Wnt5a, and we knocked-down Ror1 in MDA-MB231 cells. We measured the invasive capacity of perturbed cells to assess phenotypic changes, and mRNA was profiled to quantify gene expression changes. Differentially expressed genes were integrated into a literature-based non-canonical Wnt signaling network. The results were further used in the analysis of an independent dataset of breast cancer patients with metastasis-free survival annotation. Overexpression of the Ror2 receptor, stimulation with Wnt5a, as well as the combination of both perturbations enhanced invasiveness of MCF-7 cells. The expression-responsive targets of Ror2 overexpression in MCF-7 induced a Ror2/Wnt module of the non-canonical Wnt signaling pathway. These targets alter regulation of other pathways involved in cell remodeling processing and cell metabolism. Furthermore, the genes of the Ror2/Wnt module were assessed as a gene signature in patient gene expression data and showed an association with clinical outcome. In summary, results of this study indicate a role of a newly defined Ror2/Wnt module in breast cancer progression and present a link between Ror2 expression and increased cell invasiveness."],["dc.identifier.doi","10.3389/fonc.2017.00135"],["dc.identifier.pmid","28695110"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14538"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58892"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","2234-943X"],["dc.relation.issn","2234-943X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Ror2 Signaling and Its Relevance in Breast Cancer Progression."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","471"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Clinical & Experimental Metastasis"],["dc.bibliographiccitation.lastpage","482"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Rietkoetter, Eva"],["dc.contributor.author","Wegner, Christiane"],["dc.contributor.author","Kramer, Franz-Josef"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Stadelmann, Chr."],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2018-11-07T09:26:31Z"],["dc.date.available","2018-11-07T09:26:31Z"],["dc.date.issued","2013"],["dc.description.abstract","An essential function of the transcription factors LEF1/TCF4 in cerebral metastases of lung adenocarcinomas has been described in mouse models, suggesting a WNT/beta-catenin effect as potential mechanism. Their role in humans is still unclear, thus we analyzed LEF1, TCF4, beta-catenin, and early stage prognostic markers in 25 adenocarcinoma brain metastases using immunohistochemistry (IHC). IHC revealed nuclear TCF4 in all adenocarcinoma samples, whereas only 36 % depicted nuclear LEF1 and nuclear beta-catenin signals. Samples with nuclear LEF1 as well as high TCF4 (++++) expression were associated with a shorter survival (p = 0.01, HR = 6.68), while nuclear beta-catenin had no significant impact on prognosis and did not significantly correlate with nuclear LEF1. High proliferation index Ki67 was associated with shorter survival in late-stage disease (p = 0.03, HR 3.27). Additionally, we generated a LEF1/TCF4 as well as an AXIN2 signature, the latter as representative of WNT/beta-catenin activity, following a bioinformatics approach with a gene expression dataset of cerebral metastases in lung adenocarcinoma. To analyze the prognostic relevance in primary lung adenocarcinomas, we applied both signatures to a microarray dataset of 58 primary lung adenocarcinomas. Only the LEF1/TCF4 signature was able to separate clusters with impact on survival (p = 0.01, HR = 0.32). These clusters displayed diverging enrichment patterns of the cell cycle pathway. In conclusion, our data show that LEF1/TCF4, but not beta-catenin, have prognostic relevance in primary and cerebrally metastasized human lung adenocarcinomas. In contrast to the previous in vivo findings, these results indicate that LEF1/TCF4 act independently of beta-catenin in this setting."],["dc.identifier.doi","10.1007/s10585-012-9552-7"],["dc.identifier.isi","000317297400011"],["dc.identifier.pmid","23224985"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10341"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30319"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1573-7276"],["dc.relation.issn","0262-0898"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Nuclear LEF1/TCF4 correlate with poor prognosis but not with nuclear beta-catenin in cerebral metastasis of lung adenocarcinomas"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","285"],["dc.bibliographiccitation.journal","Oncology Research and Treatment"],["dc.bibliographiccitation.lastpage","286"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Scharf, Christian"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Dyck, Lydia"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2018-11-07T09:34:18Z"],["dc.date.available","2018-11-07T09:34:18Z"],["dc.date.issued","2014"],["dc.identifier.isi","000343816900702"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32144"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.relation.issn","2296-5262"],["dc.relation.issn","2296-5270"],["dc.title","EMMPRIN/CD147-positive tumor cell microvesicles are pro-invasive and detectable in the blood of cancer patients with metastasis"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Onkologie"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Rietkoetter, Eva"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2018-11-07T08:52:16Z"],["dc.date.available","2018-11-07T08:52:16Z"],["dc.date.issued","2011"],["dc.format.extent","151"],["dc.identifier.isi","000295160600393"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22130"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.relation.issn","0378-584X"],["dc.title","LEF1 identifies a prognostically unfavourable subgroup of lung adenocarcinoma brain metastases"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","143"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Molecular Cell Biology"],["dc.bibliographiccitation.lastpage","153"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Scharf, Christian"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Dyck, Lydia"],["dc.contributor.author","Rost, Ulrike"],["dc.contributor.author","Wenzel, Dirk"],["dc.contributor.author","Dhople, Vishnu M."],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Klemm, Florian"],["dc.date.accessioned","2018-11-07T09:58:48Z"],["dc.date.available","2018-11-07T09:58:48Z"],["dc.date.issued","2015"],["dc.description.abstract","Tumor cells secrete not only a variety of soluble factors, but also extracellular vesicles that are known to support the establishment of a favorable tumor niche by influencing the surrounding stroma cells. Here we show that tumor-derived microvesicles (T-MV) also directly influence the tumor cells by enhancing their invasion in a both autologousand heterologous manner. Neither the respective vesicle-free supernatant nor MV from benign mammary cells mediate invasion. Uptake of T-MV is essential for the proinvasive effect. We further identify the highly glycosylated form of the extracellular matrix metalloproteinase inducer (EMMPRIN) as a marker for proinvasive MV. EMMPRIN is also present at high levels on MV from metastatic breast cancer patients in vivo. Anti-EMMPRIN strategies, such as MV deglycosylation, gene knockdown, and specific blocking peptides, inhibit MV-induced invasion. Interestingly, the effect of EMMPRIN-bearing MV is not mediated by matrix metalloproteinases but by activation of the p38/MAPK signaling pathway in the tumor cells. In conclusion, T-MV stimulate cancer cell invasion via a direct feedback mechanism dependent on highly glycosylated EMMPRIN."],["dc.description.sponsorship","Deutsche Krebshilfe [109615]; DFG [BI 703/3-2]; eBIO MetastaSys (BMBF)"],["dc.identifier.doi","10.1093/jmcb/mju047"],["dc.identifier.isi","000355232100006"],["dc.identifier.pmid","25503107"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13819"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37445"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1759-4685"],["dc.relation.issn","1674-2788"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Tumor-derived microvesicles mediate human breast cancer invasion through differentially glycosylated EMMPRIN"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Onkologie"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Bayerlova, M."],["dc.contributor.author","Kramer, Franz-Josef"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Beißbarth, Tim"],["dc.date.accessioned","2018-11-07T09:04:54Z"],["dc.date.available","2018-11-07T09:04:54Z"],["dc.date.issued","2012"],["dc.format.extent","65"],["dc.identifier.isi","000310766700159"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25203"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.relation.issn","0378-584X"],["dc.title","Analyzing breast-cancer gene expression data using a newly developed graph-based WNT model in breast cancer"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1331"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","1346"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Chuang, Han-Ning"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Sieger, Dirk"],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Bayerlova, Michaela"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Schulz, Matthias"],["dc.contributor.author","Dehghani, Faramarz"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2018-11-07T09:21:57Z"],["dc.date.available","2018-11-07T09:21:57Z"],["dc.date.issued","2013"],["dc.description.abstract","The metastatic colonization of the brain by carcinoma cells is still barely understood, in particular when considering interactions with the host tissue. The colonization comes with a substantial destruction of the surrounding host tissue. This leads to activation of damage responses by resident innate immune cells to protect, repair, and organize the wound healing, but may distract from tumoricidal actions. We recently demonstrated that microglia, innate immune cells of the CNS, assist carcinoma cell invasion. Here we report that this is a fatal side effect of a physiological damage response of the brain tissue. In a brain slice coculture model, contact with both benign and malignant epithelial cells induced a response by microglia and astrocytes comparable to that seen at the interface of human cerebral metastases. While the glial damage response intended to protect the brain from intrusion of benign epithelial cells by inducing apoptosis, it proved ineffective against various malignant cell types. They did not undergo apoptosis and actually exploited the local tissue reaction to invade instead. Gene expression and functional analyses revealed that the C-X-C chemokine receptor type 4 (CXCR4) and WNT signaling were involved in this process. Furthermore, CXCR4-regulated microglia were recruited to sites of brain injury in a zebrafish model and CXCR4 was expressed in human stroke patients, suggesting a conserved role in damage responses to various types of brain injuries. Together, our findings point to a detrimental misuse of the glial damage response program by carcinoma cells resistant to glia-induced apoptosis. GLIA 2013;61:1331-1346"],["dc.identifier.doi","10.1002/glia.22518"],["dc.identifier.isi","000321983400011"],["dc.identifier.pmid","23832647"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10955"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29226"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0894-1491"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Carcinoma cells misuse the host tissue damage response to invade the brain"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","434"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Carcinogenesis"],["dc.bibliographiccitation.lastpage","442"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Chuang, Han-Ning"],["dc.contributor.author","Rietkoetter, Eva"],["dc.contributor.author","Behme, Daniel"],["dc.contributor.author","Schulz, M."],["dc.contributor.author","Schaffrinski, Meike"],["dc.contributor.author","Schindler, Stefanie"],["dc.contributor.author","Trümper, Lorenz H."],["dc.contributor.author","Kramer, Franz-Josef"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Stadelmann, C."],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2018-11-07T08:59:01Z"],["dc.date.available","2018-11-07T08:59:01Z"],["dc.date.issued","2011"],["dc.description.abstract","A role of WNT signaling for primary breast cancers of the basal-like subtype and as a predictor of brain metastasis has been described. However, a responsible WNT ligand has not been identified. To further clarify this question, we comparatively investigated 22 human breast cancer brain metastases as well as the highly invasive human breast cancer cell line MDA-MB-231 and the weakly motile MCF-7 as models for the basal-like and the luminal A subtype. WNT5A and B were found overexpressed in MDA-MB-231 cells as compared with MCF-7. This corresponded to reduction of MDA-MB-231 invasiveness by WNT inhibitors, whereas MCF-7 invasion was enhanced by recombinant WNT5B and abolished by WNT and Jun-N-terminal kinase antagonists. Expression and subcellular distribution of beta-catenin remained uninfluenced. Consistently, beta-catenin was not localized in the nuclei of brain metastases while there was strong nuclear c-Jun staining. Similar to MDA-MB-231, metastases showed expression of WNT5A/B and the alternative WNT receptors ROR1 and 2. These findings were validated using external gene expression datasets (Gene Expression Omnibus) of different breast cancer subtypes and brain metastases. Hierarchical cluster analysis yielded a close relation between basal-like cancers and brain metastases. Gene set enrichment analyses confirmed WNT pathway enrichment not only in basal-like primaries but also in cerebral metastases of all subtypes. In conclusion, WNT signaling seems highly relevant for basal-like and other subtypes of breast cancers metastasizing into the brain. beta-catenin-independent WNT signaling, presumably via ROR1-2, plays a major role in this context."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [FOR 942]"],["dc.identifier.doi","10.1093/carcin/bgq269"],["dc.identifier.isi","000288027800025"],["dc.identifier.pmid","21173432"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23785"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0143-3334"],["dc.title","beta-catenin-independent WNT signaling in basal-like breast cancer and brain metastasis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","309"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Clinical & Experimental Metastasis"],["dc.bibliographiccitation.lastpage","323"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Schmick, Nadine Annette"],["dc.contributor.author","Schubert, Antonia"],["dc.contributor.author","Rietkoetter, Eva"],["dc.contributor.author","Arackal, Jetcy"],["dc.contributor.author","Middel, Peter"],["dc.contributor.author","Schambony, Alexandra"],["dc.contributor.author","Liersch, Torsten"],["dc.contributor.author","Homayounfar, Kia"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2018-11-07T10:16:24Z"],["dc.date.available","2018-11-07T10:16:24Z"],["dc.date.issued","2016"],["dc.description.abstract","Liver metastasis development in breast cancer patients is common and confers a poor prognosis. So far, the prognostic significance of surgical resection and clinical relevance of biomarker analysis in metastatic tissue have barely been investigated. We previously demonstrated an impact of WNT signaling in breast cancer brain metastasis. This study aimed to investigate the value of established prognostic markers and WNT signaling components in liver metastases. Overall N = 34 breast cancer liver metastases (with matched primaries in 19/34 cases) were included in this retrospective study. Primaries and metastatic samples were analyzed for their expression of the estrogen (ER) and progesterone receptor, HER-2, Ki67, and various WNT signaling-components by immunohistochemistry. Furthermore, beta-catenin-dependent and -independent WNT scores were generated and analyzed for their prognostic value. Additionally, the influence of the alternative WNT receptor ROR on signaling and invasiveness was analyzed in vitro. ER positivity (HR 0.09, 95 % CI 0.01-0.56) and high Ki67 (HR 3.68, 95 % CI 1.12-12.06) in the primaries had prognostic impact. However, only Ki67 remained prognostic in the metastatic tissue (HR 2.46, 95 % CI 1.11-5.44). Additionally, the beta-catenin-independent WNT score correlated with reduced overall survival only in the metastasized situation (HR 2.19, 95 % CI 1.02-4.69, p = 0.0391). This is in line with the in vitro results of the alternative WNT receptors ROR1 and ROR2, which foster invasion. In breast cancer, the value of prognostic markers established in primary tumors cannot directly be translated to metastases. Our results revealed beta-catenin-independent WNT signaling to be associated with poor prognosis in patients with breast cancer liver metastasis."],["dc.identifier.doi","10.1007/s10585-016-9780-3"],["dc.identifier.isi","000373005900002"],["dc.identifier.pmid","26862065"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13177"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41033"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1573-7276"],["dc.relation.issn","0262-0898"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","beta-catenin-independent WNT signaling and Ki67 in contrast to the estrogen receptor status are prognostic and associated with poor prognosis in breast cancer liver metastases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","334"],["dc.bibliographiccitation.journal","BMC Bioinformatics"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Bayerlová, Michaela"],["dc.contributor.author","Jung, Klaus"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Beißbarth, Tim"],["dc.date.accessioned","2018-11-07T09:50:02Z"],["dc.date.available","2018-11-07T09:50:02Z"],["dc.date.issued","2015"],["dc.description.abstract","Background: Enrichment analysis is a popular approach to identify pathways or sets of genes which are significantly enriched in the context of differentially expressed genes. The traditional gene set enrichment approach considers a pathway as a simple gene list disregarding any knowledge of gene or protein interactions. In contrast, the new group of so called pathway topology-based methods integrates the topological structure of a pathway into the analysis. Methods: We comparatively investigated gene set and pathway topology-based enrichment approaches, considering three gene set and four topological methods. These methods were compared in two extensive simulation studies and on a benchmark of 36 real datasets, providing the same pathway input data for all methods. Results: In the benchmark data analysis both types of methods showed a comparable ability to detect enriched pathways. The first simulation study was conducted with KEGG pathways, which showed considerable gene overlaps between each other. In this study with original KEGG pathways, none of the topology-based methods outperformed the gene set approach. Therefore, a second simulation study was performed on non-overlapping pathways created by unique gene IDs. Here, methods accounting for pathway topology reached higher accuracy than the gene set methods, however their sensitivity was lower. Conclusions: We conducted one of the first comprehensive comparative works on evaluating gene set against pathway topology-based enrichment methods. The topological methods showed better performance in the simulation scenarios with non-overlapping pathways, however, they were not conclusively better in the other scenarios. This suggests that simple gene set approach might be sufficient to detect an enriched pathway under realistic circumstances. Nevertheless, more extensive studies and further benchmark data are needed to systematically evaluate these methods and to assess what gain and cost pathway topology information introduces into enrichment analysis. Both types of methods for enrichment analysis require further improvements in order to deal with the problem of pathway overlaps."],["dc.description.sponsorship","Open-Access Publikationsfonds 2015"],["dc.identifier.doi","10.1186/s12859-015-0751-5"],["dc.identifier.isi","000363615900001"],["dc.identifier.pmid","26489510"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12346"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35629"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2105"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Comparative study on gene set and pathway topology-based enrichment methods"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]