Expression of insulin-like growth factor-II, matrix metalloproteinases, and their tissue inhibitors as predictive markers in the peripheral blood of HCC patients

Hm, El Tayebi; Salah, Wafaa; Ih, El Sayed; Em, Salam; Zekri, Abdel‐Rahman N.; Zayed, Naglaa; Es, Salem; Esmat, Gamal; Abdelaziz, Ahmed Ihab

doi:10.3109/1354750x.2011.573095

Cited by 23 publications

(19 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other studies have demonstrated a significant increase in IGF-2 mRNA expression in human cirrhotic liver, in liver cancers and in the peripheral blood of HCC, in human hepatoma cell lines, in comparison to that of normal adult liver (37)(38)(39)(40). This discrepancy may be attributed to the fact that in the present study we measured only the free IGF-2 levels in serum but not mRNA.…”

Section: Discussioncontrasting

confidence: 49%

Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection

et al. 2011

View full text Add to dashboard Cite

Abstract. Hepatocellular carcinoma (HCC) contributes to 14.8% of all cancer mortality in Egypt, which has a high prevalence of hepatitis C virus (HCV). We have previously shown alterations in the insulin-like growth factor-1 (IGF-1) receptor signalling pathway during experimental hepatocarcinogenesis. The aim of this study was to determine whether serum levels of IGF-1, IGF-2 and IGFBP-3 can be used to discriminate between HCC and the stages of hepatic dysfunction in patients with liver cirrhosis assessed by the Child-Pugh (CP) score, and to correlate these levels with HCC stages. We recruited 241 subjects to the present study; 79 with liver cirrhosis, 62 with HCV-induced HCC and 100 age-matched controls. Results showed that serum levels of IGF-1, IGF-2 and IGFBP-3 were reduced significantly in cirrhosis and HCC patients in comparison to the controls, and that this reduction negatively correlated with the CP scores. However, only IGFBP-3 levels showed significant negative correlation with α-fetoprotein levels. The reduction in IGF-1 and IGFBP-3 but not IGF-2 levels was significant in HCC in comparison to patients with cirrhosis. None of the parameters significantly correlated with the HCC stage. IGFBP-3 levels discriminated between cirrhosis and HCC at a sensitivity of 87%, a specificity of 80% and a cut-off value of <682.6 ng/ ml. In conclusion, although our results showed that serum IGF-1, IGF-2 and IGFBP-3 are reduced with the progression of hepatic dysfunction, only IGFBP-3 may be considered as the most promising serological marker for the prediction of the development of HCC in the chronic HCV patients with liver cirrhosis.

show abstract

Section: Discussioncontrasting

confidence: 49%

Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Studies have (El Tayebi et al, 2011) discussed the importance of IGF-2 in HCC recurrence and prognosis, which has a high expression in liver cancer tissue. IGF-II was influenced and regulated by IGF binding protein-3, matrix metalloproteinases (MMP) and tissue inhibitor of metalloprotienase-1 (TIMP-1).…”

Section: Discussionmentioning

confidence: 99%

“…Somatostatin can combine with somatostatin receptor (SSTR) expressed by tumor cells and then inhibit promoting tumor growth hormone or cytokine's production and adjust tumor blood supply (Hasskarl et al, 2011;Jiang et al, 2011;Zhang et al, 2011;Laznicek et al, 2012;Niu et al, 2012). Insulin-like growth factor-2 (IGF-2) is an important angiogenic factor during the process which HCC induced neovascularization (El Tayebi et al, 2011;Rehem et al, 2011;Wachter et al, 2012 of HCC. At present we have not yet found the study of IGF-2 expression in serum and prognostic impact which brought by the treatment of octreotide peptide combined with TACE to liver cancer.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Association Between Insulin-like Growth Factor-2 Expression and Prognosis after Transcatheter Arterial Chemoembolization and Octreotide in Patients with Hepatocellar Carcinoma

Xiong¹,

Huang²,

Lu³

2012

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Objective: To investigate the association between the change of IGF-2 level in serum after transcatheter arterial chemoembolization (TACE) and hepatocellular carcinoma (HCC) progression, especially in relation to metastasis. Methods: IGF-2 in serum was measured by quantitative sandwich enzyme-linked immunosorbent assaybefore, 3 days and 4 weeks after TACE in 60 patients with HCC. The occurrence of HCC metastasis was also evaluated, 3 months after TACE. Results: (1) The average serum level of IGF-2 in the 60 patients with HCC was 136.5 ± 87.3 pg/ml; (2) A tendency for increase was observed with heterogenous uptake of octreotide and portal vein thrombosis. Metastatic foci were found in 37/38 patients in the group with IGF-2 increasing (97.0%), in contrast to 3/22 (13.6%) patients with IGF-2 decrease. Conclusion: The increase of IGF-2 level in serum appears to be associated with the occurrence of metastatic HCC after TACE and chemotherapy.

show abstract

“…IGF-Ⅱ was found to be overexpressed in HCC and to promote tumor cell migration, proliferation and extra-hepatic metastasis [5][6][7][8] . Moreover, our research group has shown IGF-Ⅱ to be overexpressed in peripheral blood monocytes of HCC patients, and this aberrant expression was directly correlated with elevated serum levels of alfa-fetoprotein and poor prognosis [9] . IGF-1R was reported to be upregulated in 59% of HCC tissues in which it was associated with poor prognosis and tumors exceeding the Milan criteria [10] .…”

Section: Introductionmentioning

confidence: 94%

Interplay between microRNA-17-5p, insulin-like growth factor-II through binding protein-3 in hepatocellular carcinoma

Habashy¹,

Tayebi²,

Fawzy³

et al. 2016

WJH

View full text Add to dashboard Cite

AIM:To investigate the effect of microRNA on insulinlike growth factor binding protein-3 (IGFBP-3) and hence on insulin-like growth factor-Ⅱ (IGF-Ⅱ) bioavailability in hepatocellular carcinoma (HCC). METHODS:Bioinformatic analysis was performed using microrna.org, DIANA lab and Segal lab softwares. Total RNA was extracted from 23 HCC and 10 healthy liver tissues using mirVana miRNA Isolation Kit. microRNA-17-5p (miR-17-5p) expression was mimicked and antagonized in HuH-7 cell lines using HiPerFect Basic Study 977August 18, 2016|Volume 8|Issue 23| WJH|www.wjgnet.comHabashy DA et al . miR-17-5p regulates IGF-Ⅱ via targeting IGFBP-3 Transfection Reagent, then total RNA was extracted using Biozol reagent then reverse transcribed into cDNA followed by quantification of miR-17-5p and IGFBP-3 expression using TaqMan real-time quantitative PCR. Luciferase reporter assay was performed to validate the binding of miR-17-5p to the 3'UTR of IGFBP-3. Free IGF-Ⅱ protein was measured in transfected HuH-7 cells using IGF-Ⅱ ELISA kit. RESULTS:Bioinformatic analysis revealed IGFBP-3 as a potential target for miR-17-5p. Screening of miR-17-5p and IGFBP-3 revealed a moderate negative correlation in HCC patients, where miR-17-5p was extensively underexpressed in HCC tissues (P = 0.0012), while IGFBP-3 showed significant upregulation in the same set of patients (P = 0.0041) compared to healthy donors. Forcing miR-17-5p expression in HuH-7 cell lines showed a significant downregulation of IGFBP-3 mRNA expression (P = 0.0267) and a significant increase in free IGF-Ⅱ protein (P = 0.0339) compared to mock untransfected cells using unpaired t -test. Luciferase assay validated IGFBP-3 as a direct target of miR-17-5p; luciferase activity was inhibited by 27.5% in cells co-transfected with miR-17-5p mimics and the construct harboring the wild-type binding region 2 of IGFBP-3 compared to cells transfected with this construct alone (P = 0.0474). CONCLUSION:These data suggest that regulating IGF-Ⅱ bioavailability and hence HCC progression can be achieved through targeting IGFBP-3 via manipulating the expression of miRNAs.

show abstract

Expression of insulin-like growth factor-II, matrix metalloproteinases, and their tissue inhibitors as predictive markers in the peripheral blood of HCC patients

Abstract: These results highlight the importance of profiling the expression of IGF-II, MMP-9, and TIMP-1 in the peripheral blood as prognostic molecular biomarkers in HCC.

Cited by 23 publications

References 34 publications

Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection

Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection

Association Between Insulin-like Growth Factor-2 Expression and Prognosis after Transcatheter Arterial Chemoembolization and Octreotide in Patients with Hepatocellar Carcinoma

Interplay between microRNA-17-5p, insulin-like growth factor-II through binding protein-3 in hepatocellular carcinoma

Contact Info

Product

Resources

About