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  • 1
    Online Resource
    Online Resource
    Atypical fibroxanthoma and pleomorphic dermal sarcoma – gene expression analysis compared with undifferentiated cutaneous squamous cell carcinoma
    Wiley ; 2023
    In:  JDDG: Journal der Deutschen Dermatologischen Gesellschaft Vol. 21, No. 5 ( 2023-05), p. 482-491
    Details
    In: JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Wiley, Vol. 21, No. 5 ( 2023-05), p. 482-491
    Abstract: The histogenetic origin of atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) has not been definitively elucidated. In addition to a fibroblastic origin, a keratinocytic differentiation is discussed due to strong clinical, histomorphological and molecular genetic similarities with undifferentiated cutaneous squamous cell carcinoma (cSCC). Patients and Methods 56 cases (36 AFXs, 8 PDSs, 12 undifferentiated cSCCs) were evaluated for their clinical, histomorphological, and immunohistochemical characteristics. RNA transcriptome analysis was performed on 18 cases (6 AFXs/PDSs, 6 undifferentiated cSCCs, 6 differentiated cSCCs). Results Clinically, the strong similarities in age, gender and tumor location were confirmed. Without further immunohistochemical staining, histomorphological differentiation between AFX/PDS and undifferentiated cSCC is often impossible. Principal component analysis of the RNA transcriptome analysis showed that AFX/PDS and differentiated cSCC each formed their own cluster, while the undifferentiated cSCCs fall in between these two groups, but without forming a cluster of their own. When examining differentially expressed genes (DEGs), the heat maps showed that there were cases within the undifferentiated cSCC that were more likely to be AFX/PDS than differentiated cSCC based on their expression profile. Conclusions The results provide evidence of molecular similarities between AFX/PDS and undifferentiated cSCC and suggest a common histogenetic origin.
    Type of Medium: Online Resource
    ISSN: 1610-0379 , 1610-0387
    URL: Issue
    URL: Article
    DOI: 10.1111/ddg.v21.5
    DOI: 10.1111/ddg.15006
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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    detail.hit.zdb_id: 2093479-8
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  • 2
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    A reliable transcriptomic risk-score applicable to formalin-fixed paraffin-embedded biopsies improves outcome prediction in localized prostate cancer
    Springer Science and Business Media LLC ; 2024
    In:  Molecular Medicine Vol. 30, No. 1 ( 2024-02-01)
    Details
    In: Molecular Medicine, Springer Science and Business Media LLC, Vol. 30, No. 1 ( 2024-02-01)
    Abstract: Clinical manifestation of prostate cancer (PCa) is highly variable. Aggressive tumors require radical treatment while clinically non-significant ones may be suitable for active surveillance. We previously developed the prognostic ProstaTrend RNA signature based on transcriptome‐wide microarray and RNA-sequencing (RNA-Seq) analyses, primarily of prostatectomy specimens. An RNA-Seq study of formalin-fixed paraffin-embedded (FFPE) tumor biopsies has now allowed us to use this test as a basis for the development of a novel test that is applicable to FFPE biopsies as a tool for early routine PCa diagnostics. Methods All patients of the FFPE biopsy cohort were treated by radical prostatectomy and median follow-up for biochemical recurrence (BCR) was 9 years. Based on the transcriptome data of 176 FFPE biopsies, we filtered ProstaTrend for genes susceptible to FFPE-associated degradation via regression analysis. ProstaTrend was additionally restricted to genes with concordant prognostic effects in the RNA-Seq TCGA prostate adenocarcinoma (PRAD) cohort to ensure robust and broad applicability. The prognostic relevance of the refined Transcriptomic Risk Score (TRS) was analyzed by Kaplan–Meier curves and Cox-regression models in our FFPE-biopsy cohort and 9 other public datasets from PCa patients with BCR as primary endpoint. In addition, we developed a prostate single-cell atlas of 41 PCa patients from 5 publicly available studies to analyze gene expression of ProstaTrend genes in different cell compartments. Results Validation of the TRS using the original ProstaTrend signature in the cohort of FFPE biopsies revealed a relevant impact of FFPE-associated degradation on gene expression and consequently no significant association with prognosis (Cox-regression, p-value  〉  0.05) in FFPE tissue. However, the TRS based on the new version of the ProstaTrend-ffpe signature, which included 204 genes (of originally 1396 genes), was significantly associated with BCR in the FFPE biopsy cohort (Cox-regression p-value  〈  0.001) and retained prognostic relevance when adjusted for Gleason Grade Groups. We confirmed a significant association with BCR in 9 independent cohorts including 1109 patients. Comparison of the prognostic performance of the TRS with 17 other prognostically relevant PCa panels revealed that ProstaTrend-ffpe was among the best-ranked panels. We generated a PCa cell atlas to associate ProstaTrend genes with cell lineages or cell types. Tumor-specific luminal cells have a significantly higher TRS than normal luminal cells in all analyzed datasets. In addition, TRS of epithelial and luminal cells was correlated with increased Gleason score in 3 studies. Conclusions We developed a prognostic gene-expression signature for PCa that can be applied to FFPE biopsies and may be suitable to support clinical decision-making.
    Type of Medium: Online Resource
    ISSN: 1528-3658
    URL: Article
    DOI: 10.1186/s10020-024-00789-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
    detail.hit.zdb_id: 1475577-4
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  • 3
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    Autoantibodies against NMDAR subunit NR1 disappear from blood upon anesthesia
    Elsevier BV ; 2022
    In:  Brain, Behavior, & Immunity - Health Vol. 24 ( 2022-10), p. 100494-
    Details
    In: Brain, Behavior, & Immunity - Health, Elsevier BV, Vol. 24 ( 2022-10), p. 100494-
    Type of Medium: Online Resource
    ISSN: 2666-3546
    URL: Article
    DOI: 10.1016/j.bbih.2022.100494
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 3062237-2
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  • 4
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    Characterization and evaluation of gene fusions as a measure of genetic instability and disease prognosis in prostate cancer
    Springer Science and Business Media LLC ; 2023
    In:  BMC Cancer Vol. 23, No. 1 ( 2023-06-22)
    Details
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-06-22)
    Abstract: Prostate cancer (PCa) is one of the most prevalent cancers worldwide. The clinical manifestations and molecular characteristics of PCa are highly variable. Aggressive types require radical treatment, whereas indolent ones may be suitable for active surveillance or organ-preserving focal therapies. Patient stratification by clinical or pathological risk categories still lacks sufficient precision. Incorporating molecular biomarkers, such as transcriptome-wide expression signatures, improves patient stratification but so far excludes chromosomal rearrangements. In this study, we investigated gene fusions in PCa, characterized potential novel candidates, and explored their role as prognostic markers for PCa progression. Methods We analyzed 630 patients in four cohorts with varying traits regarding sequencing protocols, sample conservation, and PCa risk group. The datasets included transcriptome-wide expression and matched clinical follow-up data to detect and characterize gene fusions in PCa. With the fusion calling software Arriba, we computationally predicted gene fusions. Following detection, we annotated the gene fusions using published databases for gene fusions in cancer. To relate the occurrence of gene fusions to Gleason Grading Groups and disease prognosis, we performed survival analyses using the Kaplan–Meier estimator, log-rank test, and Cox regression. Results Our analyses identified two potential novel gene fusions, MBTTPS2,L0XNC01::SMS and AMACR::AMACR . These fusions were detected in all four studied cohorts, providing compelling evidence for the validity of these fusions and their relevance in PCa. We also found that the number of gene fusions detected in a patient sample was significantly associated with the time to biochemical recurrence in two of the four cohorts (log-rank test, p -value  〈  0.05 for both cohorts). This was also confirmed after adjusting the prognostic model for Gleason Grading Groups (Cox regression, p -values  〈  0.05). Conclusions Our gene fusion characterization workflow revealed two potential novel fusions specific for PCa. We found evidence that the number of gene fusions was associated with the prognosis of PCa. However, as the quantitative correlations were only moderately strong, further validation and assessment of clinical value is required before potential application.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    URL: Article
    DOI: 10.1186/s12885-023-11019-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2041352-X
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  • 5
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    Online Resource
    Atypisches Fibroxanthom und pleomorphes dermales Sarkom – Genexpressionsanalyse im Vergleich zum entdifferenzierten Plattenepithelkarzinom der Haut
    Wiley ; 2023
    In:  JDDG: Journal der Deutschen Dermatologischen Gesellschaft Vol. 21, No. 5 ( 2023-05), p. 482-492
    Details
    In: JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Wiley, Vol. 21, No. 5 ( 2023-05), p. 482-492
    Abstract: Der histogenetische Ursprung des atypischen Fibroxanthoms (AFX) und pleomorphen dermalen Sarkoms (PDS) ist nicht abschließend geklärt. Neben einem fibroblastären Ursprung wird aufgrund starker klinischer, histomorphologischer und molekulargenetischer Ähnlichkeiten zum entdifferenzierten Plattenepithelkarzinom der Haut (cutaneous squamous cell carcinoma, cSCC) eine keratinozytäre Differenzierung diskutiert. Patienten und Methodik 56 Fälle (36 AFX, 8 PDS, 12 entdifferenzierte cSCC) wurden hinsichtlich ihrer klinischen, histomorphologischen und immunhistochemischen Charakteristika untersucht. An 18 Fällen (6 AFX/PDS, 6 entdifferenzierte cSCC, 6 differenzierte cSCC) wurde eine RNA‐Transkriptomanalyse durchgeführt. Ergebnisse Klinisch bestätigten sich starke Gemeinsamkeiten hinsichtlich Alter, Geschlecht und Lokalisation der Tumoren. Histomorphologisch ist es häufig ohne weiterführende immunhistochemische Färbungen nicht möglich AFX/PDS und entdifferenzierte cSCC voneinander abzugrenzen. In der Hauptkomponentenanalyse der RNA‐Transkriptomanalyse konnte gezeigt werden, dass AFX/PDS und differenzierte cSCC jeweils ein eigenes Cluster bildeten, während sich die entdifferenzierten cSCC dazwischen einordneten, ohne ein eigenes Cluster zu bilden. Bei der Betrachtung differenziell exprimierter Gene (DEG) verdeutlichten die Heat Maps , dass es innerhalb der entdifferenzierten cSCC‐Fälle gab, welche vom Expressionsprofil eher den AFX/PDS als den differenzierten cSCC zuzuordnen waren. Schlussfolgerungen Die Ergebnisse der Gesamtuntersuchungen geben Hinweise auf molekulare Ähnlichkeiten zwischen AFX/PDS und entdifferenzierten cSCC und lassen einen gemeinsamen histogenetischen Ursprung vermuten.
    Type of Medium: Online Resource
    ISSN: 1610-0379 , 1610-0387
    URL: Issue
    URL: Article
    DOI: 10.1111/ddg.v21.5
    DOI: 10.1111/ddg.15006_g
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2099463-1
    detail.hit.zdb_id: 2093479-8
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  • 6
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    The noncoding RNA LINC00152 conveys contradicting effects in different glioblastoma cells
    Springer Science and Business Media LLC ; 2021
    In:  Scientific Reports Vol. 11, No. 1 ( 2021-09-16)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-09-16)
    Abstract: Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor, characterized by its high genetic heterogeneity. In search of novel putative therapeutic RNA targets we investigated the role of the oncogenic long noncoding RNA LINC00152 (CYTOR, and STAiR18) in A172 glioblastoma cells. Here, we are the first to describe, that LINC00152 unexpectedly acts in a tumor suppressive manner in this cell line. SiRNA-based knockdown of LINC00152 enhanced malignant tumor behaviors including proliferation, cell cycle entry, migration, and invasion, contradicting previous studies using U87-MG and LN229 glioblastoma cells. Furthermore, LINC00152 knockdown had no influence on survival of A172 glioblastoma cells. In a genome wide transcription analysis of A172 and U87-MG glioblastoma cells, we identified 70 LINC00152 target genes involved in locomotion, cell migration, and motility in A172 cells, whereas in U87-MG cells only 40 target genes were detected. The LINC00152-regulated genes found in A172 differed from those identified in U87-MG glioblastoma cells, none of them being regulated in both cell lines. These findings underline the strong genetic heterogeneity of glioblastoma and point to a potential, yet unknown risk addressing LINC00152 lncRNA as a prospective therapeutic target in GBM.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-021-97533-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 7
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    Online Resource
    Stroke, Seizures, Hallucinations and Postoperative Delirium as Neurological Complications after Cardiac Surgery and Percutaneous Valve Replacement
    MDPI AG ; 2022
    In:  Journal of Cardiovascular Development and Disease Vol. 9, No. 11 ( 2022-10-24), p. 365-
    Details
    In: Journal of Cardiovascular Development and Disease, MDPI AG, Vol. 9, No. 11 ( 2022-10-24), p. 365-
    Abstract: (1) Background: Neurological complications such as acute ischemic stroke or postoperative delirium are frequent after cardiac surgery or percutaneous valve replacement. This study aimed to identify corresponding risk factors. (2) Methods: 297 patients with percutaneous valve replacement or cardiac surgery were postoperatively screened for neurological complications such as delirium, stroke, seizures and hallucinations twice daily for three days. Pre- and perioperative risk factors were evaluated in a multivariate model. (3) Results: Neurological complications occurred in 43.8% (n = 130) as composed of delirium (43.43%, n = 129), stroke (2.7%, n = 8), seizures (1.35%, n = 4) and real hallucinations (3.36%, n = 10). Multiple logistic regression revealed an association of neurological complications with lower Montreal Cognitive Assessment scores (Exp(B) 2.042; 95% CI, 1.183–3.525, p = 0.010), older age (Exp(B) 1.071; 95% CI, 1.036–1.107, p 〈 0.001), red blood cell transfusions until postoperative day 3 (Exp(B) 1.157; 95% CI, 1.030–1.300, p = 0.014), history of heart failure (Exp(B) 1.985; 95% CI, 1.130–3.487, p = 0.017) and increased CRP levels (Exp(B) 1.004; 95% CI, 1.000–1.008, p = 0.037). (4) Conclusions: Postoperative delirium remains a frequent complication after cardiac surgery, while stroke and seizures occur rarely. A preoperative risk profile including older age, history of heart failure and cognitive impairment was identified for a complicated postoperative course. However, the impact of an intense inflammatory response must not be neglected.
    Type of Medium: Online Resource
    ISSN: 2308-3425
    URL: Article
    DOI: 10.3390/jcdd9110365
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2777082-5
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