Type I insulin-like growth factor as a liver reserve assessment tool in hepatocellular carcinoma

Abdel-Wahab, Reham; Shehata, Samir; Hassan, Manal M.; Habra, Mouhammed Amir; Eskandari, Ghazaleh; Tinkey, Peggy T.; Mitchell, Jennifer; Lee, Ju-Seog; Amin, Hesham M.; Kaseb, Ahmed O.

doi:10.2147/jhc.s81309

Cited by 14 publications

(13 citation statements)

References 146 publications

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“…Most likely, these findings can be attributed to the fact that treatment with DEN, with or without PLE, produces substantial liver necrosis with progressive fibrosis and cirrhosis; thus, decreased IGF1 levels correlated with decreased functional capacity of the liver in the DEN-treated pigs. We expected that, as IGF1 levels decreased, GH levels would increase because of the negative feedback effects of the decreased IGF1 levels on the pituitary gland, similar to recent observations reported by our group [30]. Our current study, however, did not demonstrate a negative correlation between GH and IGF1.…”

Section: Discussionsupporting

confidence: 89%

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Validation of a Preclinical Model of Diethylnitrosamine-Induced Hepatic Neoplasia in Yucatan Miniature Pigs

et al. 2016

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Objective: The purpose of this study was to reduce the time to tumor onset in a diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) swine model via partial liver embolization (PLE) and to characterize the model for use in translational research. Methods: Eight Yucatan miniature pigs were injected intraperitoneally with either saline (n = 2) or DEN (n = 6) solution weekly for 12 weeks. Three of the DEN-treated pigs underwent PLE. The animals underwent periodic radiological evaluation, liver biopsy, and blood sampling, and full necropsy was performed at study termination (∼29 months). Results: All DEN-treated pigs developed hepatic adenoma and HCC. PLE accelerated the time to adenoma development but not to HCC development. Biomarker analysis results showed that IGF1 levels decreased in all DEN-treated pigs as functional liver capacity decreased with progression of HCC. VEGF and IL-6 levels were positively correlated with disease progression. Immunohistochemical probing of HCC tissues demonstrated the expression of several important survival-promoting proteins. Conclusion: To our knowledge, we are the first to demonstrate an accelerated development of hepatic neoplasia in Yucatan miniature pigs. Our HCC swine model closely mimics the human condition (i.e., progressive disease stages and expression of relevant molecular markers) and is a viable translational model.

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Section: Discussionsupporting

confidence: 89%

“…For instance, recent findings from our group suggest that the GHR/IGF1 signaling axis plays an important role in HCC [30]. In our current study, the expression of GHR and IGF1R was very pronounced in the HCC tissue from DEN-treated pigs.…”

Section: Discussionsupporting

confidence: 53%

Validation of a Preclinical Model of Diethylnitrosamine-Induced Hepatic Neoplasia in Yucatan Miniature Pigs

et al. 2016

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“…Some case–control studies have supported a positive association between the insulin-like growth factor-1 (IGFI) level and the risk of liver cancer [ 2 – 4 ]. Indeed, in clinical practice, IGFI is used to assess HCC reserve capacity [ 5 , 6 ] and as a prognostic marker for HCC progression and survival [ 3 ]. However, further research is needed.…”

Section: Introductionmentioning

confidence: 99%

Serum insulin-like growth factor-1 and its binding protein 3 as prognostic factors for the incidence, progression, and outcome of hepatocellular carcinoma: a systematic review and meta-analysis

Wang

Deng

et al. 2017

Oncotarget

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PurposePrevious studies have supported an association between serum insulin-like growth factor-1 (IGF1) and IGF-binding protein 3 (IGFBP3) levels and hepatocellular carcinoma (HCC), but the results were inaccurate. It has recently been proposed that IGF1 and IGFBP3 play roles in the time-to-progression (TTP) and overall survival (OS) of HCC patients. Our results revealed that serum IGF1 level is predictive of the progression and survival of HCC patients.ResultsHCC was associated with a significant reduction in serum IGF-1 and IGFBP-3 levels compared to cirrhosis (p = 0.037). Low serum IGF1 levels were predictive of a shorter TTP (OR, 2.74; 95% confidence interval [CI], 1.92–3.90) and poorer OS (odds ratio [OR], 2.20; 95% CI, 1.81–2.68) in HCC patients. The IGF1/IGFBP3 molar ratio was not significantly associated with the risk of HCC (OR, 1.311; 95% CI, 0.761–2.260).Materials and MethodsWe conducted a comprehensive literature search in PubMed, EMBASE, and the Cochrane Library. Twenty studies met the inclusion criteria and were subjected to statistical analysis. The geometric mean and standard deviation (SD) of serum IGF1 and IGFBP3 levels in the healthy, cirrhosis, and HCC groups were calculated. Pooled odds ratios (ORs) were calculated using a fixed-effects model to analyse the association of serum IGF1 level with the progression and survival of HCC patients.ConclusionsSerum IGF1 and IGFBP3 levels were positively associated with the incidence of HCC. Serum IGF1 level is an independent prognostic factor for the progression and survival of HCC patients.

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“…Moreover, serum IGF-1 levels varied in patients based on their CTP classes. Cirrhotic patients with preserved liver functions defined as CTP class A tended to have higher IGF-1 levels than patients with advanced-stage CTP class B and C. 11 , 33 Therefore, serum IGF-1 has been considered as a surrogate marker for hepatic reserve in cirrhotic patients. Consistent with these findings, we found that IGF-1 levels changed significantly according to the presence or absence of cirrhosis of the patients in our study, Table 5 .…”

Section: Discussionmentioning

confidence: 99%

“…The relationship between IGF-1 level and hepatic function has been reported by several studies that demonstrated the correlation between the severity of cirrhosis and the development of HCC and low serum IGF-1 concentration. 11 – 13 Furthermore, the levels of IGF-1 are significantly lower in patients with cirrhosis CTP C than CTP A and B. Additionally, correlation with other advanced cirrhotic and portal hypertension parameters such as albumin level, INR value, and spleen size also has been reported. 14 – 16 Similarly, a significant decrease in IGF-1 concentration was observed in patients with advanced HCC.…”

Section: Introductionmentioning

confidence: 95%

<p>Prognostic Significance of Serum Insulin-Like Growth Factor-1 in Hepatocellular Cancer Patients: A Validation Study</p>

Laçin

Yalçın

Karakaş

et al. 2020

JHC

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Background The Child–Turcotte–Pugh score (CTP) is the most commonly used tool to assess hepatic reserve and predict survival in hepatocellular cancer (HCC). The CTP stratification accuracy has been questioned and attempts have been made to improve the objectivity of the system. Serum insulin-like growth factor-1 (IGF-1)-CTP has been proposed to improve CTP prognostic accuracy. We aimed to validate the IGF-CTP score in our patient population. Patients and Methods A total of 84 diagnosed HCC patients were enrolled prospectively. IGF-CTP scores in addition to CTP scores were calculated. C-index was used to compare the prognostic significance of the two scoring systems and overall survival (OS). Results Cirrhosis was present in 48 (57.1%) patients, 35 (41.7%) patients were non-cirrhotic, 36 (42.8%) patients were hepatitis B (HBV) positive, and 8 (9.5%) patients were hepatitis C (HCV) positive. Serum IGF-1 levels were significantly lower in cirrhotic compared with non-cirrhotic patients (p=0.04). There was a significant difference in OS rates of patients with serum IGF-1 level <50 ng/mL and patients with serum IGF-1 levels ≥50 ng/mL (p=0.02); the OS rates were 6.5 and 14.8 months, respectively (p=0.02). The median OS of all patients was 7.38 months (95% CI: 5.89–13.79). The estimated C-index for CTP and IGF-CTP scores was 0.605 (95% CI: 0.538, 0.672) and 0.599 (95% CI: 0.543, 0.655), respectively. The U statistics indicated that the C-indices between two scoring systems are not statistically different (P= 0.91). Conclusion This study evaluated IGF-1 levels and the IGF-CTP classification in a predominantly HBV (+) cohort of HCC patients with 41.7% non-cirrhotic. Although the prognostic value was similar, among patients with CTP-A, class those reclassified as IGF-CTP B had shorter OS than those with IGF-CTP score A. Thus, further validations of IGF-CTP score in similar populations may add additional value as a stratification tool to predict HCC outcome.

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Type I insulin-like growth factor as a liver reserve assessment tool in hepatocellular carcinoma

Cited by 14 publications

References 146 publications

Validation of a Preclinical Model of Diethylnitrosamine-Induced Hepatic Neoplasia in Yucatan Miniature Pigs

Validation of a Preclinical Model of Diethylnitrosamine-Induced Hepatic Neoplasia in Yucatan Miniature Pigs

Serum insulin-like growth factor-1 and its binding protein 3 as prognostic factors for the incidence, progression, and outcome of hepatocellular carcinoma: a systematic review and meta-analysis

<p>Prognostic Significance of Serum Insulin-Like Growth Factor-1 in Hepatocellular Cancer Patients: A Validation Study</p>

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