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  • 1
    Online Resource
    Online Resource
    A novel circulating miRNA panel for non-invasive ovarian cancer diagnosis and prognosis
    Springer Science and Business Media LLC ; 2022
    In:  British Journal of Cancer Vol. 127, No. 8 ( 2022-11-01), p. 1550-1556
    Details
    In: British Journal of Cancer, Springer Science and Business Media LLC, Vol. 127, No. 8 ( 2022-11-01), p. 1550-1556
    Abstract: Ovarian cancer (OC) is an aggressive disease, primarily diagnosed in late stages with only 20% of patients surviving more than 5 years after diagnosis. There is a pending need to improve current diagnostics and prognostics. Methods In this study, we investigated total circulating cell-free microRNA (cf-miRNA) levels as well as a panel of cf-miRNAs in the plasma of OC patients ( n  = 100), patients with benign lesions ( n  = 45) and healthy controls ( n  = 99). Results High levels of cf-miRNAs correlated with unfavourable clinical features and were an independent prognosticator of patient survival. By mining NGS data, we identified a signature panel of seven individual cf-miRNAs which could distinguish controls from benign cases with an AUC of 0.77 and controls from cancer cases with an AUC of 0.87. Importantly, in combination with the current gold-standard marker, CA-125, the panel could predict early OC with an AUC of 0.93. Conclusion Our findings highlight the potential of cf-miRNA levels as well as individual cf-miRNAs for OC diagnosis and prognosis that warrants further clinical evaluation.
    Type of Medium: Online Resource
    ISSN: 0007-0920 , 1532-1827
    URL: Article
    DOI: 10.1038/s41416-022-01925-0
    RVK:
    XA 33500
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2002452-6
    detail.hit.zdb_id: 80075-2
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  • 2
    Online Resource
    Online Resource
    Total circulating microRNA level as an independent prognostic marker for risk stratification in breast cancer
    Springer Science and Business Media LLC ; 2022
    In:  British Journal of Cancer Vol. 127, No. 1 ( 2022-07-01), p. 156-162
    Details
    In: British Journal of Cancer, Springer Science and Business Media LLC, Vol. 127, No. 1 ( 2022-07-01), p. 156-162
    Abstract: Although breast cancer (BC) has a high survival rate, relapse events may occur which ultimately lead to aggressive disease. Circulating cell-free microRNAs (cf-miRNAs) are a promising minimally invasive biomarker with diagnostic and/or prognostic potential. Unfortunately, there is still no consensus as to a universal cf-miRNA biomarker in BC and there has been no clinical implementation until now. One major limitation is the technical variation with cf-miRNA isolation and specific quantification methods. Methods In this study, we assessed the total levels of cf-miRNAs as a potential prognostic marker for BC in 356 plasma samples from 250 BC patients. Results High levels of cf-miRNAs significantly correlated with unfavourable clinical features including tumour stage, load and the presence of metastasis at diagnosis. With more than 9 years of follow-up, we could show that global cf-miRNA levels significantly correlated with cancer relapse which was confirmed in multivariate cox regression analysis. Finally, for a subset of patients where the serial plasma was available, levels of cf-miRNAs increased in the plasma prior to clinical detection of progressive disease and were massively elevated in patients who died compared to those still alive at the last timepoint of measurement. Conclusions This is the first study to suggest that total cf-miRNA levels in the blood can be used as an independent prognostic marker for BC.
    Type of Medium: Online Resource
    ISSN: 0007-0920 , 1532-1827
    URL: Article
    DOI: 10.1038/s41416-022-01756-z
    RVK:
    XA 33500
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2002452-6
    detail.hit.zdb_id: 80075-2
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  • 3
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    Online Resource
    Circulating cf-miRNA as a more appropriate surrogate liquid biopsy marker than cfDNA for ovarian cancer
    Springer Science and Business Media LLC ; 2023
    In:  Scientific Reports Vol. 13, No. 1 ( 2023-04-04)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-04-04)
    Abstract: Ovarian cancer (OC) is an aggressive disease, primarily diagnosed in late stages with only 20% of patients surviving more than 5 years. Liquid biopsy markers have great potential to improve current diagnostic and prognostic methods. Here, we compared miRNAs and DNA methylation in matched plasma, whole blood and tissues as a surrogate marker for OC. We found that while both cfDNA and cf-miRNAs levels were upregulated in OC compared to patients with benign lesions or healthy controls, only cf-miRNA levels were an independent prognosticator of survival. Following on our previous work, we found members of the miR-200 family, miR-200c and miR-141 to be upregulated in both plasma and matched tissues of OC patients which correlated with adverse clinical features. We could also show that the upregulation of miR-200c and -141 correlated with promoter DNA hypomethylation in tissues, but not in plasma or matched whole blood samples. As cf-miRNAs are more easily obtained and very stable in blood, we conclude that they might serve as a more appropriate surrogate liquid biopsy marker than cfDNA for OC.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-023-32243-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2615211-3
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  • 4
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    Online Resource
    Evaluation of Storage Tubes for Combined Analysis of Circulating Nucleic Acids in Liquid Biopsies
    MDPI AG ; 2019
    In:  International Journal of Molecular Sciences Vol. 20, No. 3 ( 2019-02-06), p. 704-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 20, No. 3 ( 2019-02-06), p. 704-
    Abstract: In the last decade, circulating nucleic acids such as microRNAs (miRNAs) and cell-free DNA (cfDNA) have become increasingly important in serving as potential novel biomarkers for a variety of human diseases. If cell-free nucleic acids are to become routinely used in diagnostics, the difference in plasma miRNA and cfDNA levels between healthy and diseased subjects must exceed pre-analytical and analytical variability. Until now, few studies have addressed the time limitations of pre-processing or explored the potential use of long-term blood storage tubes, which might need to be implemented in real-life diagnostics. In this study, we analyzed the stability of four breast cancer-associated miRNAs and two cancer-associated genes under various storage conditions, to test their limitations for potential application in clinical diagnostics. In two consecutive experiments, we tested the limits of conventional EDTA tubes, as well as long-term storage blood collection tubes (BCTs) from four different manufacturers. We found that circulating miRNAs are relatively stable when stored in EDTA monovettes for up to 12 h before processing. When stored in BCTs, circulating miRNAs and cfDNA are stable for up to 7 days, depending on the manufacturer. Norgen tubes were superior for cfDNA yield, while Streck tubes performed the worst in our study with hemolysis induction. In conclusion, plasma prepared from whole blood is suitable for the quantification of both cf-miRNAs and cfDNA simultaneously.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms20030704
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
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    Online Resource
    Potential of blood-based biomarker approaches in endometrium and breast cancer: a case-control comparison study
    Springer Science and Business Media LLC ; 2022
    In:  Archives of Gynecology and Obstetrics Vol. 306, No. 5 ( 2022-03-13), p. 1623-1632
    Details
    In: Archives of Gynecology and Obstetrics, Springer Science and Business Media LLC, Vol. 306, No. 5 ( 2022-03-13), p. 1623-1632
    Abstract: Endometrial carcinoma is the second most common gynecological malignancy. Until today lacking a screening tool. A blood-based biomarker could help address this need. Methods The expression levels of 30 acylcarnitines, 18 amino acids, 6 miRNAs, and 7 DNA methylation sites were measured in blood samples from 331 women (20 EC, 14 benign uterine lesions (benign), 140 breast cancers (BC), 157 controls). Areas under the ROC curves (AUC), sensitivity (sens.) and specificity (spec.) were computed to identify the variables best distinguishing. Results The best top ten markers for the four comparisons (cancer vs. cancer-free; EC vs. BC, EC vs. controls; EC vs. benign), were identified via AUC. Malonylcarnitine distinguished best patients with EC from controls (AUC: 0.827, sens. 80%, spec. 73.1%) or BC (AUC: 0.819, sens. 84.3%, spec. 80%) being most notable. Tryptophan best differentiated benign from EC (AUC: 0.846, sens. 70%, spec. 92.9%). Conclusions The levels of the analyzed blood markers yielded promising results in the detection of EC and warrant further evaluation.
    Type of Medium: Online Resource
    ISSN: 1432-0711
    URL: Article
    DOI: 10.1007/s00404-022-06482-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1458450-5
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  • 6
    Online Resource
    Online Resource
    Table_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-9-20)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-9-20)
    Abstract: Selective uptake of (18)F-fluoro-ethyl-tyrosine ( 18 F-FET) is used in high-grade glioma (HGG) to assess tumor metabolic activity via positron emission tomography (PET). We aim to investigate its value for target volume definition, as a prognosticator, and associations with whole-blood transcriptome liquid biopsy (WBT lbx) for which we recently reported feasibility to mirror tumor characteristics and response to particle irradiation in recurrent HGG (rHGG). Methods 18 F-FET-PET data from n = 43 patients with primary glioblastoma (pGBM) and n = 33 patients with rHGG were assessed. pGBM patients were irradiated with photons and sequential proton/carbon boost, and rHGG patients were treated with carbon re-irradiation (CIR). WBT (Illumina HumanHT-12 Expression BeadChips) lbx was available for n = 9 patients from the rHGG cohort. PET isocontours (40%–70% SUVmax, 10% steps) and MRI-based treatment volumes (MRIvol) were compared using the conformity index (CI) (pGBM, n = 16; rHGG, n = 27). Associations with WBT lbx data were tested on gene expression level and inferred pathways activity scores (PROGENy) and from transcriptome estimated cell fractions (CIBERSORT, xCell). Results In pGBM, median SUVmax was higher in PET acquired pre-radiotherapy (4.1, range (R) 1.5–7.8; n = 20) vs. during radiotherapy (3.3, R 1.5–5.7, n = 23; p = 0.03) and in non-resected (4.7, R 2.9–7.9; n = 11) vs. resected tumors (3.3, R 1.5–7.8, n = 32; p = 0.01). In rHGG, a trend toward higher SUVmax values in grade IV tumors was observed (p = 0.13). Median MRIvol was 32.34 (R 8.75–108.77) cm 3 in pGBM (n = 16) and 20.77 (R 0.63–128.44) cm 3 in rHGG patients (n = 27). The highest median CI was observed for 40% (pGBM, 0.31) and 50% (rHGG, 0.43, all tumors) isodose, with 70% (40%) isodose in grade III (IV) rHGG tumors (median CI, 0.38 and 0.49). High SUVmax was linked to shorter survival in pGBM ( & gt;3.3, p = 0.001, OR 6.0 [2.1–17.4]) and rHGG ( & gt;2.8, p = 0.02, OR 4.1 [1.2–13.9]). SUVmax showed associations with inferred monocyte fractions, hypoxia, and TGFbeta pathway activity and links to immune checkpoint gene expression from WBT lbx. Conclusion The benefits of 18 F-FET-PET imaging on gross tumor volume (GTV) definition for particle radiotherapy warrant further evaluation. SUVmax might assist in prognostic stratification of HGG patients for particle radiotherapy, highlights heterogeneity in rHGG, and is positively associated with unfavorable signatures in peripheral whole-blood transcriptomes.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.901390
    DOI: 10.3389/fonc.2022.901390.s001
    DOI: 10.3389/fonc.2022.901390.s002
    DOI: 10.3389/fonc.2022.901390.s003
    DOI: 10.3389/fonc.2022.901390.s004
    DOI: 10.3389/fonc.2022.901390.s005
    DOI: 10.3389/fonc.2022.901390.s006
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 7
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    Online Resource
    Whole Blood Transcriptional Fingerprints of High-Grade Glioma and Longitudinal Tumor Evolution under Carbon Ion Radiotherapy
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 3 ( 2022-01-28), p. 684-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 3 ( 2022-01-28), p. 684-
    Abstract: Purpose: To assess the value of whole blood transcriptome data from liquid biopsy (lbx) in recurrent high-grade glioma (rHGG) patients for longitudinal molecular monitoring of tumor evolution under carbon ion irradiation (CIR). Methods: Whole blood transcriptome (WBT) analysis (Illumina HumanHT-12 Expression BeadChips) was performed in 14 patients with rHGG pre re-irradiation (reRT) with CIR and 3, 6 and 9 weeks post-CIR (reRT grade III:5, 36%, IV:9, 64%). Patients were irradiated with 30, 33, 36 GyRBE (n = 5, 6, 3) in 3GyRBE per fraction. Results: WTB analysis showed stable correlation with treatment characteristics and patients tumor grade, indicating a preserved tumor origin specific as well as dynamic transcriptional fingerprints of peripheral blood cells. Initial histopathologic tumor grade was indirectly associated with TMEM173 (STING), DNA-repair (ATM, POLD4) and hypoxia related genes. DNA-repair, chromatin remodeling (LIG1, SMARCD1) and immune response (FLT3LG) pathways were affected post-CIR. Longitudinal WTB fingerprints identified two distinct trajectories of rHGG evolution, characterized by differential and prognostic CRISPLD2 expression pre-CIR. Conclusions: Lbx based WTB analysis holds the potential for molecular stratification of rHGG patients and therapy monitoring. We demonstrate the feasibility of the peripheral blood transcriptome as a sentinel organ for identification of patient, tumor characteristics and CIR specific fingerprints in rHGG.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14030684
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 8
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    Online Resource
    AAMP is a binding partner of costimulatory human B7-H3
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Advances Vol. 4, No. 1 ( 2022-01-01)
    Details
    In: Neuro-Oncology Advances, Oxford University Press (OUP), Vol. 4, No. 1 ( 2022-01-01)
    Abstract: Targeted immunotherapies are of growing interest in the treatment of various cancers. B7 homolog 3 protein (B7-H3), a member of the co-stimulatory/-inhibitory B7-family, exerts immunosuppressive and pro-tumorigenic functions in various cancer types and is under evaluation in ongoing clinical trials. Unfortunately, interaction partner(s) remain unknown which restricts the druggability. Methods Aiming to identify potential binding partner(s) of B7-H3, a yeast two-hybrid and a mass spectrometry screen were performed. Potential candidates were evaluated by bimolecular fluorescence complementation (BiFC) assay, co-immunoprecipitation (co-IP), and functionally in a 3H-thymidine proliferation assay of Jurkat cells, a T-cell lineage cell line. Prognostic value of angio-associated migratory cell protein (AAMP) and B7-H3 expression was evaluated in isocitrate dehydrogenase 1 wildtype (IDH1wt) glioblastoma (GBM) patients from The Cancer Genome Atlas (TCGA)-GBM cohort. Results Of the screening candidates, CD164, AAMP, PTPRA, and SLAMF7 could be substantiated via BiFC. AAMP binding could be further confirmed via co-IP and on a functional level. AAMP was ubiquitously expressed in glioma cells, immune cells, and glioma tissue, but did not correlate with glioma grade. Finally, an interaction between AAMP and B7-H3 could be observed on expression level, hinting toward a combined synergistic effect. Conclusions AAMP was identified as a novel interaction partner of B7-H3, opening new possibilities to create a targeted therapy against the pro-tumorigenic costimulatory protein B7-H3.
    Type of Medium: Online Resource
    ISSN: 2632-2498
    URL: Article
    DOI: 10.1093/noajnl/vdac098
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 3009682-0
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