Skip to main content
Erschienen in: Medical Oncology 4/2015

01.04.2015 | Original Paper

Overexpression of AGGF1 is correlated with angiogenesis and poor prognosis of hepatocellular carcinoma

verfasst von: Wei Wang, Guang-Yao Li, Jian-Yu Zhu, Da-Bing Huang, Hang-Cheng Zhou, Wen Zhong, Chu-Shu Ji

Erschienen in: Medical Oncology | Ausgabe 4/2015

Einloggen, um Zugang zu erhalten

Abstract

Angiogenic factor with G-patch and FHA domains 1 (AGGF1) is a factor implicating in vascular differentiation and angiogenesis. Several lines of evidence indicate that aberrant expression of AGGF1 is associated with tumor initiation and progression. The aim of this study was to investigate the expression and prognostic value of AGGF1 in hepatocellular carcinoma (HCC), as well as its relationship with clinicopathological factors and tumor angiogenesis. Immunohistochemistry was performed to evaluate the expression of AGGF1 in HCC and paracarcinomatous tissues collected from 70 patients. Vascular endothelial growth factor (VEGF) and CD34 expression levels were examined in the 70 HCC tissues. Prognostic significance of tumoral AGGF1 expression was determined. Notably, AGGF1 expression was significantly higher in HCC than in surrounding non-tumor tissues (65.7 vs. 25.7 %; P < 0.001). AGGF1 expression was significantly correlated with tumoral VEGF expression and CD34-positive microvessel density. Moreover, AGGF1 expression was significantly associated with tumor size, tumor capsule, vascular invasion, Edmondson grade, alpha-fetoprotein level, and TNM stage. Kaplan–Meier survival analysis showed that high AGGF1 was correlated with reduced overall survival (OS) rate (P = 0.001) and disease-free survival (DFS) rate (P < 0.001). Multivariate analysis identified AGGF1 as an independent poor prognostic factor of OS and DFS in HCC patients (P = 0.043 and P = 0.010, respectively). Taken together, increased AGGF1 expression is associated with tumor angiogenesis and serves as an independent unfavorable prognostic factor for OS and DFS in HCC. AGGF1 may represent a potential therapeutic target for HCC.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.CrossRefPubMed Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.CrossRefPubMed
2.
Zurück zum Zitat Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
3.
Zurück zum Zitat Blechacz B, Mishra L. Hepatocellular carcinoma biology. Recent Results Cancer Res. 2013;190:1–20.CrossRefPubMed Blechacz B, Mishra L. Hepatocellular carcinoma biology. Recent Results Cancer Res. 2013;190:1–20.CrossRefPubMed
4.
5.
Zurück zum Zitat Bishayee A, Darvesh AS. Angiogenesis in hepatocellular carcinoma: a potential target for chemoprevention and therapy. Curr Cancer Drug Targets. 2012;12:1095–118.PubMed Bishayee A, Darvesh AS. Angiogenesis in hepatocellular carcinoma: a potential target for chemoprevention and therapy. Curr Cancer Drug Targets. 2012;12:1095–118.PubMed
6.
Zurück zum Zitat Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86:353–64.CrossRefPubMed Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86:353–64.CrossRefPubMed
7.
Zurück zum Zitat Muto J, Shirabe K, Sugimachi K, Maehara Y. Review of angiogenesis in hepatocellular carcinoma. Hepatol Res. 2015;45:1–9.CrossRefPubMed Muto J, Shirabe K, Sugimachi K, Maehara Y. Review of angiogenesis in hepatocellular carcinoma. Hepatol Res. 2015;45:1–9.CrossRefPubMed
8.
Zurück zum Zitat Finsterbusch T, Steinfeldt T, Doberstein K, Rodner C, Mankertz A. Interaction of the replication proteins and the capsid protein of porcine circovirus type 1 and 2 with host proteins. Virology. 2009;386:122–31.CrossRefPubMed Finsterbusch T, Steinfeldt T, Doberstein K, Rodner C, Mankertz A. Interaction of the replication proteins and the capsid protein of porcine circovirus type 1 and 2 with host proteins. Virology. 2009;386:122–31.CrossRefPubMed
9.
Zurück zum Zitat Tian XL, Kadaba R, You SA, Liu M, Timur AA, Yang L, et al. Identification of an angiogenic factor that when mutated causes susceptibility to Klippel–Trenaunay syndrome. Nature. 2004;427:640–5.CrossRefPubMedCentralPubMed Tian XL, Kadaba R, You SA, Liu M, Timur AA, Yang L, et al. Identification of an angiogenic factor that when mutated causes susceptibility to Klippel–Trenaunay syndrome. Nature. 2004;427:640–5.CrossRefPubMedCentralPubMed
10.
Zurück zum Zitat Hu Y, Li L, Seidelmann SB, Timur AA, Shen PH, Driscoll DJ, et al. Identification of association of common AGGF1 variants with susceptibility for Klippel–Trenaunay syndrome using the structure association program. Ann Hum Genet. 2008;72:636–43.CrossRefPubMedCentralPubMed Hu Y, Li L, Seidelmann SB, Timur AA, Shen PH, Driscoll DJ, et al. Identification of association of common AGGF1 variants with susceptibility for Klippel–Trenaunay syndrome using the structure association program. Ann Hum Genet. 2008;72:636–43.CrossRefPubMedCentralPubMed
11.
Zurück zum Zitat Chen D, Li L, Tu X, Yin Z, Wang Q. Functional characterization of Klippel–Trenaunay syndrome gene AGGF1 identifies a novel angiogenic signaling pathway for specification of vein differentiation and angiogenesis during embryogenesis. Hum Mol Genet. 2013;22:963–76.CrossRefPubMed Chen D, Li L, Tu X, Yin Z, Wang Q. Functional characterization of Klippel–Trenaunay syndrome gene AGGF1 identifies a novel angiogenic signaling pathway for specification of vein differentiation and angiogenesis during embryogenesis. Hum Mol Genet. 2013;22:963–76.CrossRefPubMed
12.
Zurück zum Zitat Lu Q, Yao Y, Yao Y, Liu S, Huang Y, Lu S, et al. Angiogenic factor AGGF1 promotes therapeutic angiogenesis in a mouse limb ischemia model. PLoS One. 2012;7:e46998.CrossRefPubMedCentralPubMed Lu Q, Yao Y, Yao Y, Liu S, Huang Y, Lu S, et al. Angiogenic factor AGGF1 promotes therapeutic angiogenesis in a mouse limb ischemia model. PLoS One. 2012;7:e46998.CrossRefPubMedCentralPubMed
13.
Zurück zum Zitat Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954;7:462–503.CrossRefPubMed Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954;7:462–503.CrossRefPubMed
14.
Zurück zum Zitat Sun QK, Zhu JY, Wang W, Lv Y, Zhou HC, Yu JH, et al. Diagnostic and prognostic significance of peroxiredoxin 1 expression in human hepatocellular carcinoma. Med Oncol. 2014;31:786.CrossRefPubMed Sun QK, Zhu JY, Wang W, Lv Y, Zhou HC, Yu JH, et al. Diagnostic and prognostic significance of peroxiredoxin 1 expression in human hepatocellular carcinoma. Med Oncol. 2014;31:786.CrossRefPubMed
15.
Zurück zum Zitat Kudo Y, Ogawa I, Kitajima S, Kitagawa M, Kawai H, Gaffney PM, et al. Periostin promotes invasion and anchorage-independent growth in the metastatic process of head and neck cancer. Cancer Res. 2006;66:6928–35.CrossRefPubMed Kudo Y, Ogawa I, Kitajima S, Kitagawa M, Kawai H, Gaffney PM, et al. Periostin promotes invasion and anchorage-independent growth in the metastatic process of head and neck cancer. Cancer Res. 2006;66:6928–35.CrossRefPubMed
16.
Zurück zum Zitat Fan C, Ouyang P, Timur AA, He P, You SA, Hu Y, et al. Novel roles of GATA1 in regulation of angiogenic factor AGGF1 and endothelial cell function. J Biol Chem. 2009;284:23331–43.CrossRefPubMedCentralPubMed Fan C, Ouyang P, Timur AA, He P, You SA, Hu Y, et al. Novel roles of GATA1 in regulation of angiogenic factor AGGF1 and endothelial cell function. J Biol Chem. 2009;284:23331–43.CrossRefPubMedCentralPubMed
17.
Zurück zum Zitat Liu Y, Yang H, Song L, Li N, Han QY, Tian C, et al. AGGF1 protects from myocardial ischemia/reperfusion injury by regulating myocardial apoptosis and angiogenesis. Apoptosis. 2014;19:1254–68.CrossRefPubMed Liu Y, Yang H, Song L, Li N, Han QY, Tian C, et al. AGGF1 protects from myocardial ischemia/reperfusion injury by regulating myocardial apoptosis and angiogenesis. Apoptosis. 2014;19:1254–68.CrossRefPubMed
18.
Zurück zum Zitat Xu Y, Zhou M, Wang J, Zhao Y, Li S, Zhou B, et al. Role of microRNA-27a in down-regulation of angiogenic factor AGGF1 under hypoxia associated with high-grade bladder urothelial carcinoma. Biochim Biophys Acta. 2014;1842:712–25.CrossRefPubMed Xu Y, Zhou M, Wang J, Zhao Y, Li S, Zhou B, et al. Role of microRNA-27a in down-regulation of angiogenic factor AGGF1 under hypoxia associated with high-grade bladder urothelial carcinoma. Biochim Biophys Acta. 2014;1842:712–25.CrossRefPubMed
19.
Zurück zum Zitat Roe OD, Anderssen E, Sandeck H, Christensen T, Larsson E, Lundgren S. Malignant pleural mesothelioma: genome-wide expression patterns reflecting general resistance mechanisms and a proposal of novel targets. Lung Cancer. 2010;67:57–68.CrossRefPubMed Roe OD, Anderssen E, Sandeck H, Christensen T, Larsson E, Lundgren S. Malignant pleural mesothelioma: genome-wide expression patterns reflecting general resistance mechanisms and a proposal of novel targets. Lung Cancer. 2010;67:57–68.CrossRefPubMed
20.
Zurück zum Zitat Tanigawa N, Lu C, Mitsui T, Miura S. Quantitation of sinusoid-like vessels in hepatocellular carcinoma: its clinical and prognostic significance. Hepatology. 1997;26:1216–23.PubMed Tanigawa N, Lu C, Mitsui T, Miura S. Quantitation of sinusoid-like vessels in hepatocellular carcinoma: its clinical and prognostic significance. Hepatology. 1997;26:1216–23.PubMed
21.
Zurück zum Zitat Kaya M, Wada T, Akatsuka T, Kawaguchi S, Nagoya S, Shindoh M, et al. Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis. Clin Cancer Res. 2000;6:572–7.PubMed Kaya M, Wada T, Akatsuka T, Kawaguchi S, Nagoya S, Shindoh M, et al. Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis. Clin Cancer Res. 2000;6:572–7.PubMed
22.
Zurück zum Zitat Yoshiji H, Kuriyama S, Noguchi R, Yoshii J, Ikenaka Y, Yanase K, et al. Angiopoietin 2 displays a vascular endothelial growth factor dependent synergistic effect in hepatocellular carcinoma development in mice. Gut. 2005;54:1768–75.CrossRefPubMedCentralPubMed Yoshiji H, Kuriyama S, Noguchi R, Yoshii J, Ikenaka Y, Yanase K, et al. Angiopoietin 2 displays a vascular endothelial growth factor dependent synergistic effect in hepatocellular carcinoma development in mice. Gut. 2005;54:1768–75.CrossRefPubMedCentralPubMed
23.
Zurück zum Zitat Major MB, Roberts BS, Berndt JD, Marine S, Anastas J, Chung N, et al. New regulators of Wnt/beta-catenin signaling revealed by integrative molecular screening. Sci Signal. 2008;1:ra12.PubMed Major MB, Roberts BS, Berndt JD, Marine S, Anastas J, Chung N, et al. New regulators of Wnt/beta-catenin signaling revealed by integrative molecular screening. Sci Signal. 2008;1:ra12.PubMed
24.
Zurück zum Zitat Easwaran V, Lee SH, Inge L, Guo L, Goldbeck C, Garrett E, et al. beta-Catenin regulates vascular endothelial growth factor expression in colon cancer. Cancer Res. 2003;63:3145–53.PubMed Easwaran V, Lee SH, Inge L, Guo L, Goldbeck C, Garrett E, et al. beta-Catenin regulates vascular endothelial growth factor expression in colon cancer. Cancer Res. 2003;63:3145–53.PubMed
Metadaten
Titel
Overexpression of AGGF1 is correlated with angiogenesis and poor prognosis of hepatocellular carcinoma
verfasst von
Wei Wang
Guang-Yao Li
Jian-Yu Zhu
Da-Bing Huang
Hang-Cheng Zhou
Wen Zhong
Chu-Shu Ji
Publikationsdatum
01.04.2015
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 4/2015
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-015-0574-2

Weitere Artikel der Ausgabe 4/2015

Medical Oncology 4/2015 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.