Dataset Information

Global proteome changes in liver tissue 6 weeks after FOLFOX treatment of colorectal cancer liver metastases.

ABSTRACT: Study: Oxaliplatin-based chemotherapy for colorectal liver metastasis is associated with sinusoidal injury of liver parenchyma and may result in increased morbidity after liver surgery. Preclinical and human liver parenchyma studies have proposed several pathways of oxaliplatin-induced injury, but the effects on protein level remains unknown. Protein expression in liver tissue from eight patients treated with FOLFOX and seven controls without treatment was analyzed by label-free liquid chromatography mass spectrometry. Conclusion: Six weeks after FOLFOX treatment less than 1% of identified proteins showed changes in expression. The changes were associated with DNA replication, cell cycle entry and innate immune response. We hypothesize that the changes are residual after recovery from FOLFOX treatment injury.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver

DISEASE(S): Colon Cancer

SUBMITTER: Mario Oroshi

LAB HEAD: Jacek R Wisniewski

PROVIDER: PXD001889 | Pride | 2016-12-14

REPOSITORIES: pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20130122_EXQ4_JRW_B52_1_L.raw	Raw
	20130122_EXQ4_JRW_B52_1_T.raw	Raw
	20130122_EXQ4_JRW_B52_2_L.raw	Raw
	20130122_EXQ4_JRW_B52_2_T.raw	Raw
	20130122_EXQ4_JRW_B53_1_L.raw	Raw

Items per page:

1 - 5 of 81

Similar Datasets

Project description:Chronic liver injury promotes fibrosis, which can progress to cirrhosis, a major cause of morbidity and mortality worldwide. Resolving the cell-type-specific transcriptional changes orchestrating this transformation remains challenging. Recent advances in differentiation protocols allow the generation of multi-lineage human liver organoids (HLOs) from human pluripotent stem cells (hPSCs), providing a new model system to study evolving liver injury. We differentiated hPSCs into HLOs and defined optimal 3D culture conditions for liver injury induction. We modeled steatohepatitis through treatment with palmitic acid (PA) and fibrotic injury through treatment with transforming growth factor beta 1 (TGF-β1). For each injury type, we evaluated the development of fibrosis and inflammation by monitoring changes in morphology, gene expression, and histology. We then performed single-cell RNA-sequencing (scRNA-seq) to investigate cell-type diversity in healthy organoids at different time-points and to understand how TGF-β1- and PA-mediated injury affects each cell type. We observed transcriptional response signatures in injured HLOs to be both cell-type- and injury-specific. TGF-β1 treatment expanded hepatic stellate cell (HSC)-like populations and remodeled cell-cycle patterning. Gene set scoring revealed increased fibroblast activity with TGF-β1 treatment, while PA treatment was associated with inflammatory activity. Differential gene expression analysis at the subpopulation level showed induced profibrotic and extracellular matrix-remodeling pathways with TGF-β1 and non-alcoholic fatty liver disease (NAFLD) expression signatures with PA treatment. Evaluation of receptor and ligand expression defined hepatocyte-, cholangiocyte-, and HSC-like cell-cell interactions induced upon TGF-β1 treatment, an effect not observed with PA treatment. Tracing the changes at receptor-ligand pair resolution revealed specific COL1A1-Integrin complex interactions with TGF-β1 treatment and inflammation-specific interactions including CXCR7 and HLA-C with PA treatment. Treatment of HLOs with PA and TGF-β1 also demonstrated a sequential increase in expression of gene sets that predict clinical disease progression in non-alcoholic steatohepatitis (NASH). Our results demonstrate the applicability of hPSC-derived HLOs as a dynamic in vitro 3D human liver model system for the study of fibrotic and inflammatory liver injury.

Dataset Information

Global proteome changes in liver tissue 6 weeks after FOLFOX treatment of colorectal cancer liver metastases.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets