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Inter-patient heterogeneity in the hepatic ischemia-reperfusion injury transcriptome: Implications for research and diagnostics
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SYSNO ASEP 0582382 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Inter-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 authors 13 Source Title New Biotechnology. - : Elsevier - ISSN 1871-6784
Roč. 79, MAR 25 2024 (2024), s. 20-29Number of pages 10 s. Language eng - English Country NL - Netherlands Keywords Gene expression ; Microarray ; Transplantation medicine ; Pre-analytical workflows Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemical research methods Method of publishing Open access Institutional support BTO-N - RVO:86652036 UT WOS 001140534100001 EID SCOPUS 85179623154 DOI 10.1016/j.nbt.2023.12.001 Annotation Cellular 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. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2024 Electronic address https://www.sciencedirect.com/science/article/pii/S1871678423000699?via%3Dihub
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