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| Status |
Public on Feb 21, 2024 |
| Title |
Inter-patient heterogeneity in the hepatic ischemia-reperfusion injury transcriptome: implications for research and diagnostics [MUG data] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Background & Aims: Cellular responses induced by surgical procedure or ischemia-reperfusion injury (IRI) may severely alter transcriptome profiles. We have investigated this effect to obtain insight into molecular ischemia responses during surgical procedures and characterize pre-analytical effects impacting on molecular analyses. Methods: 143 non-malignant liver samples were obtained from 30 patients at different time points of ischemia during surgery from two individual cohorts, treated either with the Pringle maneuver or total vascular exclusion. Transcriptomics profiles were analyzed by Affymetrix microarrays and expression of selected mRNAs was validated by RT-qPCR. Results: Transcriptional profiles of both cohorts displayed 179 genes that were mutually deregulated confirming elevated cytokine signaling, and NFkB as the dominant pathways in ischemia response. Contrary to ischemia, reperfusion induced pro-apoptotic and pro-inflammatory cascades involving TNF, NFkB 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 clearly present in the non-tumor tissue. Conclusions: We identified transcripts mutually deregulated during ischemia and reperfusion injury in both cohorts that can be used to monitor ischemia during liver surgery and highlight the importance of pre-analytical quality control. The marked inter-patient variability might reflect differences in individual stress responses and impact of underlying disease conditions. Furthermore, we provide a comprehensive and pre-analytically highly standardized in vivo transcriptome profile of histologically normal liver and identified 230 genes with substantial pre-analytical robustness (<2 % covariation across both cohorts) that might serve as reference genes and could be particularly suited for future diagnostic applications. Conclusions: We identified transcripts mutually deregulated during ischemia and reperfusion injury in both cohorts that can be used to monitor ischemia during liver surgery and highlight the importance of pre-analytical quality control. The marked inter-patient variability might reflect differences in individual stress responses and impact of underlying disease conditions. Furthermore, we provide a comprehensive and pre-analytically highly standardized in vivo transcriptome profile of histologically normal liver and identified 230 genes with substantial pre-analytical robustness (<2 % covariation across both cohorts) that might serve as reference genes and could be particularly suited for future diagnostic applications.
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| Overall design |
Ischemia related changes of RNA profiles obtained from frozen liver tissue samples collected before, during and after routine surgery and compared between the different time points. Medical University of Graz, 83 samples of a total of 21 patients at 4 different time points per patient.
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/38072306/
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| Contributor(s) |
Groiss S, Viertler C, Kap M, Bernhardt G, Mischinger H, Sieuwerts A, Verhoef C, Riegman P, Kruhoffer M, Svec D, Sjöback R, Becker K, Zatloukal K |
| Citation(s) |
38072306 |
| Submission date |
Apr 03, 2023 |
| Last update date |
Feb 22, 2024 |
| Contact name |
Silvia Groiss |
| Organization name |
Medical University of Graz
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| Department |
Institute of Pathology
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| Street address |
Neue Stiftingtalstraße 6
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| City |
Graz |
| ZIP/Postal code |
8010 |
| Country |
Austria |
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| Platforms (1) |
| GPL13667 |
[HG-U219] Affymetrix Human Genome U219 Array |
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| Samples (83)
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| This SubSeries is part of SuperSeries: |
| GSE228783 |
Inter-patient heterogeneity in the hepatic ischemia-reperfusion injury transcriptome: implications for research and diagnostics |
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| Relations |
| BioProject |
PRJNA951628 |
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