IGFBP-1 and IGF-I as markers for advanced fibrosis in NAFLD – a pilot study

Hagström, Hannes; Stål, Per; Hultcrantz, Rolf; Brismar, Kerstin; Ansurudeen, Ishrath

doi:10.1080/00365521.2017.1379556

Cited by 38 publications

(37 citation statements)

References 40 publications

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“…Emerging evidence suggests a critical role of apolipoproteins, including APOA4, in the pathogenesis of NAFLD Specifically, Kang et al demonstrated that over‐expression of APOA4 promotes lipid accumulation in the liver, and Qin et al reported that the level of APOA4 protein was increased in the genetically obese ( ob/ob ) mice. Furthermore, a marked upregulation of APOA4, as well as SERPINE1 and IGFBP1, has been demonstrated in patients with NAFLD.…”

Section: Discussionmentioning

confidence: 99%

“…In agreement with this, we identified several cancer‐related over‐expressed genes, including Cscbp2 , Apoa4 , Anxa2 , Serpine1 , Igfbp1 , and Tubb2a , that were associated with chromatin‐accessible regions in NASH‐derived HCC. It has been reported that up‐regulation of these genes may have significance in the hepatocarcinogenic process, in general, and in the pathogenesis of NAFLD and NAFLD‐associated liver carcinogenesis, in particular …”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that up-regulation of these genes may have significance in the hepatocarcinogenic process, in general, [39][40][41][42][43][44] and in the pathogenesis of NAFLD and NAFLD-associated liver carcinogenesis, in particular. [45][46][47][48][49] Apoa4 is a critical gene involved in the regulation of multiple metabolic pathways, including lipid absorption, lipid metabolism, and glucose homeostasis. 47 protein was increased in the genetically obese (ob/ob) mice.…”

Section: Discussionmentioning

confidence: 99%

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Identification of chromatin‐accessible domains in non‐alcoholic steatohepatitis‐derived hepatocellular carcinoma

Dechassa

Tryndyak

Conti

et al. 2018

Molecular Carcinogenesis

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Non-alcoholic steatohepatitis (NASH) is becoming one of the major causes of hepatocellular carcinoma (HCC) in the United States and Western countries; however, the molecular mechanisms associated with NASH-related liver carcinogenesis are not well understood. In the present study, we investigated cancer-associated chromatin alterations using a model that resembles the development of NASH-related HCC in humans. An assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) identified 1677 tumor-specific chromatin-accessible regions in NASH-derived HCC tissue samples. Using a combined analysis of ATAC-seq and global gene expression data, we identified 199 differentially expressed genes, 139 up-regulated and 60 down-regulated. Interestingly, 15 of the 139 up-regulated genes had accessible chromatin sites within 5 Kb of the transcription start site (TSS), including Apoa4, Anxa2, Serpine1, Igfbp1, and Tubb2a, genes critically involved in the development of NASH and HCC. We demonstrate that the mechanism for the up-regulation of these genes is associated with the enrichment of chromatin-accessible regions by transcription factors, especially NFATC2, and histone H3K4me1 and H3K27ac gene transcription-activating marks. These data underline the important role of chromatin accessibility perturbations in reshaping of the chromatin landscape in NASH-related HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Identification of chromatin‐accessible domains in non‐alcoholic steatohepatitis‐derived hepatocellular carcinoma

Dechassa

Tryndyak

Conti

et al. 2018

Molecular Carcinogenesis

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“…This “ideal test” would help clinicians identify and follow‐up patients with NASH, predicting the response to therapy and the risk of disease progression . Many studies have identified potential biomarkers to predict disease activity for the whole spectrum of NAFLD: a) cell death and apoptosis biomarkers, including caspase‐generated CK‐18 fragment (CK‐18); b) the fibroblast growth factor 21 (FGF21); c) insulin‐like growth factor 2 (IGF‐2) and the epidermal growth factor receptor (EGFR) . These biomarkers are expected to improve the ability to stratify disease severity in NAFLD and may identify additional pathways to target for treatment .…”

Section: The Need For Reliable Biomarkersmentioning

confidence: 99%

“…9,21 In addition, there is also a need to develop and validate a simple, F I G U R E 1 Extrahepatic complications of non-alcoholic fatty liver disease (FGF21); c) insulin-like growth factor 2 (IGF-2) and the epidermal growth factor receptor (EGFR). [25][26][27][28][29] These biomarkers are expected to improve the ability to stratify disease severity in NAFLD and may identify additional pathways to target for treatment. 28 However, despite several available studies, an accurate and reproducible noninvasive method to diagnose NAFLD/NASH, which could be used for screening in the general population or for patient follow-up has still not been identified.…”

Section: The Need For Reliable Biomarkersmentioning

confidence: 99%

Global epidemiology of non‐alcoholic fatty liver disease/non‐alcoholic steatohepatitis: What we need in the future

Araújo

Rosso

Bedogni

et al. 2018

Liver International

348

250

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The estimated prevalence of non‐alcoholic fatty liver disease (NAFLD) worldwide is approximately 25%. However, the real prevalence of NAFLD and the associated disorders is unknown mainly because reliable and applicable diagnostic tests are lacking. This is further complicated by the lack of consensus on the terminology of different entities such as NAFLD or nonalcoholic steatohepatitis (NASH). Although assessing fatty infiltration in the liver is simple by ultrasound, the gold standard for the assessment of fibrosis, the only marker of progression towards more severe liver disease is still liver biopsy. Although other non‐invasive tests have been proposed, they must still be validated in large series. Because NAFL/NAFLD/NASH and related metabolic diseases represent an economic burden, finding an inexpensive method to diagnose and stage fatty liver is a priority. A translational approach with the use of cell and/or animal models could help to reach this goal.

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SOMAscan Proteomics Identifies Serum Biomarkers Associated With Liver Fibrosis in Patients With NASH

Luo

Wadhawan

Greenfield

et al. 2021

Hepatology Communications

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Nonalcoholic steatohepatitis (NASH) is a major cause of liver-related morbidity and mortality worldwide. Liver fibrosis stage, a key component of NASH, has been linked to the risk of mortality and liver-related clinical outcomes. Currently there are no validated noninvasive diagnostics that can differentiate between fibrosis stages in patients with NASH; many existing tests do not reflect underlying disease pathophysiology. Noninvasive biomarkers are needed to identify patients at high-risk of NASH with advanced fibrosis. This was a retrospective study of patients with histologically proven NASH with fibrosis stages 0-4. The SOMAscan proteomics platform was used to quantify 1,305 serum proteins in a discovery cohort (n = 113). In patients with advanced (stages 3-4) versus early fibrosis (stages 0-2), 97 proteins with diverse biological functions were differentially expressed. Next, fibrosis-stage classification models were explored using a machine learning-based approach to prioritize the biomarkers for further evaluation. A four-protein model differentiated patients with stage 0-1 versus stage 2-4 fibrosis (area under the receiver operating characteristic curve [AUROC] = 0.74), while a 12-protein classifier differentiated advanced versus early fibrosis (AUROC = 0.83). Subsequently, the model's performance was validated in two independent cohorts (n = 71 and n = 32) with similar results (AUROC = 0.74-0.78). Our advanced fibrosis model performed similarly to or better than Fibrosis-4 index, aspartate aminotransferase-to-platelet ratio index, and nonalcoholic fatty liver disease (NAFLD) fibrosis score-based models for all three cohorts. Conclusion: A SOMAscan proteomics-based exploratory classifier for advanced fibrosis, consisting of biomarkers that reflect the complexity of NASH pathophysiology, demonstrated similar performance in independent validation cohorts and performed similarly or better than Fibrosis-4 index, aspartate aminotransferase-toplatelet ratio index, and NAFLD fibrosis score. Further studies are warranted to evaluate the clinical utility of these biomarker panels in patients with NAFLD. (Hepatology Communications 2021;0:1-14).

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IGFBP-1 and IGF-I as markers for advanced fibrosis in NAFLD – a pilot study

Abstract: This pilot study suggests an association between serum IGFBP-1 and IGF-I levels with advanced fibrosis in NAFLD patients. IGFBP1 and IGF-1 could be of interest as future biomarkers. Similar studies in larger cohorts are needed.

Cited by 38 publications

References 40 publications

Identification of chromatin‐accessible domains in non‐alcoholic steatohepatitis‐derived hepatocellular carcinoma

Identification of chromatin‐accessible domains in non‐alcoholic steatohepatitis‐derived hepatocellular carcinoma

Global epidemiology of non‐alcoholic fatty liver disease/non‐alcoholic steatohepatitis: What we need in the future

SOMAscan Proteomics Identifies Serum Biomarkers Associated With Liver Fibrosis in Patients With NASH

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