Unravelling the genetic determinants of sinusoidal obstruction syndrome: an integrative multi-omics approach
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PROVIDER: PRJNA739371 | ENA |
REPOSITORIES: ENA
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Project description:We used bulk RNAseq to analyze gene expression changes in six lymphoblastoid cell lines before and after incubation with busulfan
2023-06-15 | GSE178497 | GEO
Project description:The purpose of the study is to determine whether anticoagulant use (i.e. salicylates, clopidogrel, low-molecular weight heparin, or coumarin derivates) is able to prevent the development of the sinusoidal obstruction syndrome secondary to oxaliplatin-based neoadjuvant chemotherapy in patients suffering from colorectal liver metastases.
| 2071144 | ecrin-mdr-crc
Project description:Model Establishment of Mice with Oxaliplatin-induced Hepatic Sinusoidal Obstruction Syndrome
| PRJNA872386 | ENA
Project description:BackgroundGenotype-phenotype analyses of rare diseases often suffer from a lack of power, due to small sample size, which makes identifying significant associations difficult. Sinusoidal obstruction syndrome (SOS) of the liver is a rare but life-threatening complication of hematopoietic stem cell transplantation (HSCT). The alkylating agent busulfan is commonly used in HSCT and known to trigger SOS. We developed a novel pipeline to identify genetic determinants in rare diseases by combining in vitro information with clinical whole-exome sequencing (WES) data and applied it in SOS patients and controls.MethodsFirst, we analysed differential gene expression in six lymphoblastoid cell lines (LCLs) before and after incubation with busulfan. Second, we used WES data from 87 HSCT patients and estimated the association with SOS at the SNP and the gene levels. We then combined the results of the expression and the association analyses into an association statistic at the gene level. We used an over-representation analysis to functionally characterize the genes that were associated with a significant combined test statistic.ResultsAfter treatment of LCLs with busulfan, 1708 genes were significantly up-, and 1385 down-regulated. The combination of the expression experiment and the association analysis of WES data into a single test statistic revealed 35 genes associated with the outcome. These genes are involved in various biological functions and processes, such as "Cell growth and death", "Signalling molecules and interaction", "Cancer", and "Infectious disease".ConclusionsThis novel data analysis pipeline integrates two independent omics datasets and increases statistical power for identifying genotype-phenotype associations. The analysis of the transcriptomics profile of cell lines treated with busulfan and WES data from HSCT patients allowed us to identify potential genetic contributors to SOS. Our pipeline could be useful for identifying genetic contributors to other rare diseases where limited power renders genome-wide analyses unpromising.Trial registrationFor the clinical dataset: Clinicaltrials.gov: NCT01257854. https://clinicaltrials.gov/ct2/history/NCT01257854.
| S-EPMC10075428 | biostudies-literature
Project description:Sinusoidal obstruction syndrome (SOS; formerly veno-occlusive disease) is a well-established complication of hematopoietic stem cell transplantation, pyrrolizidine alkaloid intoxication, and widely used chemotherapeutic agents such as oxaliplatin. It is associated with substantial morbidity and mortality. Pathogenesis of SOS in humans is poorly understood. To explore its molecular mechanisms, we used Affymetrix U133 Plus 2.0 microarrays to investigate the gene expression profile of 11 human livers with oxaliplatin-related SOS and compared it to 12 matched controls. Hierarchical clustering analysis showed that profiles from SOS and controls formed distinct clusters. To identify functional networks and gene ontologies, data were analyzed by the Ingenuity Pathway Analysis Tool. A total of 913 genes were differentially expressed in SOS: 613 being upregulated and 300 downregulated. Reverse transcriptase-PCR results showed excellent concordance with microarray data. Pathway analysis showed major gene upregulation in six pathways in SOS compared with controls: acute phase response (notably interleukin 6), coagulation system (Serpine1, THBD, and VWF), hepatic fibrosis/hepatic stellate cell activation (COL3a1, COL3a2, PDGF-A, TIMP1, and MMP2), and oxidative stress. Angiogenic factors (VEGF-C) and hypoxic factors (HIF1A) were upregulated. The most significant increase was seen in CCL20 mRNA. In conclusion, oxaliplatin-related SOS can be readily distinguished according to morphologic characteristics but also by a molecular signature. Global gene analysis provides new insights into mechanisms underlying chemotherapy-related hepatotoxicity in humans and potential targets relating to its diagnosis, prevention, and treatment. Activation of VEGF and coagulation (vWF) pathways could partially explain at a molecular level the clinical observations that bevacizumab and aspirin have a preventive effect in SOS. This dataset is part of the TransQST collection.
2012-01-18 | E-MTAB-503 | biostudies-arrayexpress
Project description:To further explore to mechanisms of oxaliplatin-induced hepatic sinusodial obstruction syndrome, we established a mouse model of OXA-induced HSOS and the difference of mRNA expression level between normal mice and model mice was detected.
2022-09-01 | GSE211859 | GEO
Project description:Urethra was partially ligated and the urinary bladder was removed 10 days or 6 weeks after obstruction. Sham operated rats were used as controls. An addtitonal group of rats were repoerated 6 weeks after surgery and the obstruction was removed. These rats were then sacrificed 10 days after deobstruction. The bladder (including the urothelium) was frozen and used for RNA extraction. Urinary bladders from sham-operated, 10 days and 6 weeks after obstruction and rats 10 days after deobstruction were compared. mRNA and microRNA were both analyzed.
2013-11-24 | E-GEOD-47080 | biostudies-arrayexpress
Project description:To find miRNAs that involve in renal epithelial transition and renal fibrosis, we performed unilateral ureteral obstruction of mice for 7 days. After that, we harvested kidneys, and performed microarray of miRNA. Contralateral kidneys without ureteral obstruction were used as controls. miRNAs were purified from kidneys with ureteral obstruction and contralateral kidneys without ureteral obstruction. Then microarray of miRNA was performed (n=4). miRNAs up-regulated in kidneys with ureteral obsctruction compared with contralateral kidneys were sorted. We performed unilateral ureteral obstruction of mice for 7 days, and harvested kidneys.
2012-12-05 | E-GEOD-42716 | biostudies-arrayexpress
Project description:To find miRNAs that involve in renal epithelial transition and renal fibrosis, we performed unilateral ureteral obstruction of mice for 7 days. After that, we harvested kidneys, and performed microarray of miRNA. Contralateral kidneys without ureteral obstruction were used as controls. miRNAs were purified from kidneys with ureteral obstruction and contralateral kidneys without ureteral obstruction. Then microarray of miRNA was performed (n=4). miRNAs up-regulated in kidneys with ureteral obsctruction compared with contralateral kidneys were sorted.
2012-12-05 | GSE42716 | GEO
Project description:Urethra was partially ligated and the urinary bladder was removed 10 days or 6 weeks after obstruction. Sham operated rats were used as controls. An addtitonal group of rats were repoerated 6 weeks after surgery and the obstruction was removed. These rats were then sacrificed 10 days after deobstruction. The bladder (including the urothelium) was frozen and used for RNA extraction.
2013-11-24 | GSE47080 | GEO