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Inter-patient heterogeneity in the hepatic ischemia-reperfusion injury transcriptome: Implications for research and diagnostics

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    SYSNO ASEP0582382
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleInter-patient heterogeneity in the hepatic ischemia-reperfusion injury transcriptome: Implications for research and diagnostics
    Author(s) Groiss, S. (DE)
    Viertler, C. (AT)
    Kap, M. (NL)
    Bernhardt, G. (AT)
    Mischinger, H. (AT)
    Sieuwerts, A. (NL)
    Verhoef, C. (NL)
    Riegman, P. (NL)
    Kruhoffer, M. (DK)
    Švec, David (BTO-N) RID
    Sjoeback, S. R. (SE)
    Becker, K. (DE)
    Zatloukal, K. (AT)
    Number of authors13
    Source TitleNew Biotechnology. - : Elsevier - ISSN 1871-6784
    Roč. 79, MAR 25 2024 (2024), s. 20-29
    Number of pages10 s.
    Languageeng - English
    CountryNL - Netherlands
    KeywordsGene expression ; Microarray ; Transplantation medicine ; Pre-analytical workflows
    Subject RIVEB - Genetics ; Molecular Biology
    OECD categoryBiochemical research methods
    Method of publishingOpen access
    Institutional supportBTO-N - RVO:86652036
    UT WOS001140534100001
    EID SCOPUS85179623154
    DOI10.1016/j.nbt.2023.12.001
    AnnotationCellular responses induced by surgical procedure or ischemia-reperfusion injury (IRI) may severely alter tran-scriptome profiles and complicate molecular diagnostics. To investigate this effect, we characterized such pre-analytical effects in 143 non-malignant liver samples obtained from 30 patients at different time points of ischemia during surgery from two individual cohorts treated either with the Pringle manoeuvre or total vascular exclusion. Transcriptomics profiles were analyzed by Affymetrix microarrays and expression of selected mRNAs was validated by RT-PCR. We found 179 mutually deregulated genes which point to elevated cytokine signaling with NF kappa B as a dominant pathway in ischemia responses. In contrast to ischemia, reperfusion induced pro-apoptotic and pro-inflammatory cascades involving TNF, NF kappa B and MAPK pathways. FOS and JUN were down-regulated in steatosis compared to their up-regulation in normal livers. Surprisingly, molecular signatures of underlying primary and secondary cancers were present in non-tumor tissue. The reported inter-patient variability might reflect differences in individual stress responses and impact of underlying disease conditions. Furthermore, we provide a set of 230 pre-analytically highly robust genes identified from histologically normal livers (<2% covariation across both cohorts) that might serve as reference genes and could be particularly suited for future diagnostic applications.
    WorkplaceInstitute of Biotechnology
    ContactMonika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700
    Year of Publishing2024
    Electronic addresshttps://www.sciencedirect.com/science/article/pii/S1871678423000699?via%3Dihub
Number of the records: 1  

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