Dataset Information

Identification of serum insulin-like growth factor binding protein 1 as diagnostic biomarker for early-stage alcohol-induced liver disease.

ABSTRACT:

Background

Alcohol consumption is a major cause of liver disease in humans. The use and monitoring of biomarkers associated with early, pre-clinical stages of alcohol-induced liver disease (pre-ALD) could facilitate diagnosis and treatment, leading to improved outcomes.

Methods

We investigated the pathological, transcriptomic and protein changes in early stages of pre-ALD in mice fed the Lieber-Decarli liquid diet with or without alcohol for four months to identify biomarkers for the early stage of alcohol induced liver injury. Mice were sampled after 1, 2 and 4 months treatment.

Results

Pathological examination revealed a modest increase in fatty liver changes in alcohol-treated mice. Transcriptomics revealed gene alterations at all time points. Most notably, the Igfbp1 (Insulin-Like Growth Factor Binding Protein 1) was selected as the best candidate gene for early detection of liver damage since it showed early and continuously enhanced induction during the treatment course. Consistent with the microarray data, both Igfbp1mRNA expression in the liver tissue and the IGFBP1 serum protein levels showed progressive and significant increases over the course of pre-ALD development.

Conclusions

The results suggest that in conjunction with other tests, serum IGFBPI protein could provide an easily measured biomarker for early detection of alcohol-induced liver injury in humans.

SUBMITTER: Li HH

PROVIDER: S-EPMC4016206 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Publications

Identification of serum insulin-like growth factor binding protein 1 as diagnostic biomarker for early-stage alcohol-induced liver disease.

Li Heng-Hong HH Doiron Kathryn K Patterson Andrew D AD Gonzalez Frank J FJ Fornace Albert J AJ

Journal of translational medicine 20131023

<h4>Background</h4>Alcohol consumption is a major cause of liver disease in humans. The use and monitoring of biomarkers associated with early, pre-clinical stages of alcohol-induced liver disease (pre-ALD) could facilitate diagnosis and treatment, leading to improved outcomes.<h4>Methods</h4>We investigated the pathological, transcriptomic and protein changes in early stages of pre-ALD in mice fed the Lieber-Decarli liquid diet with or without alcohol for four months to identify biomarkers for ...[more]

PMID: 24152801

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Project description:BackgroundMalnutrition and muscle wasting are common features frequently observed in pancreatic ductal adenocarcinoma (PDAC) patients with cancer cachexia. They are associated with reduced survival and quality of life. Nutrition therapy is an important part of multimodal cancer care in PDAC. However, due to the complexity of nutrition assessment, only 30-60% of patients with nutritional risks receive nutritional treatment at present. It is important to identify biomarkers that may be used to improve management of PDAC-associated malnutrition. Serum insulin-like growth factor binding protein 2 (IGFBP2) has emerged as a potential serum biomarker in a variety of tumours. However, its association with malnutrition and muscle wasting in PDAC is unclear.MethodsWe evaluated the tumour IGFBP2 expression and serum IGFBP2 level in 98 PDAC patients using immunohistochemistry and enzyme-linked immunosorbent assay and analysed the correlation between them. Furthermore, we explored the relationship between IGFBP2 of both tumour and serum and nutritional status (Patient-Generated Subjective Global Assessment and skeletal muscle index). Pan02 IGFBP2 stable transfection cell lines, Pan02 PLV-IGFBP2 cells, and PLKO-IGFBP2 cells were injected subcutaneously into the flank of C57BL/6 mouse. Serum IGFBP2 levels, food intake, and body weight of these mice were measured. The degree of muscle atrophy is characterized by haematoxylin and eosin, Oil Red O, and Masson's trichrome staining. The mRNA and protein expression of several essential muscle-related signal proteins such as atrogin-1 and muscle RING finger 1 was measured.ResultsAmong 98 patients, we found that tumour IGFBP2 expression is related to plasma IGFBP2 levels (rs = 0.562, P < 0.001), and they significantly increased among patients with Patient-Generated Subjective Global Assessment ≥9 and correlated with overall survival. Moreover, serum IGFBP2 level is negatively correlated with skeletal muscle index (rs = -0.600, P < 0.001) and Hounsfield units (rs = -0.532, P < 0.001). In mice injected with Pan02 PLV-IGFBP2 cell, circulating IGFBP2 was elevated while body weight and food intake were decreased when compared with Pan02 PLV-Control group. These mice also exhibited significantly aggravated muscle fibre atrophy, lipid deposition, and increased collagen tissue, and the expression of mRNA and protein of atrogin-1 and muscle RING finger 1 in the gastrocnemius muscle is increased. Conversely, these symptoms were alleviated in the PLKO-IGFBP2 group.ConclusionsIn the current study, there is a significant correlation between serum IGFBP2 levels, malnutrition, and muscle atrophy in PDAC. Our results suggested that serum IGFBP2 level might be a promising biomarker and intervention targets for PDAC-associated severe malnutrition and muscle wasting.

Dataset Information

Identification of serum insulin-like growth factor binding protein 1 as diagnostic biomarker for early-stage alcohol-induced liver disease.

Background

Methods

Results

Conclusions

Publications

Identification of serum insulin-like growth factor binding protein 1 as diagnostic biomarker for early-stage alcohol-induced liver disease.

Similar Datasets

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