Skip to main content
Erschienen in: Tumor Biology 3/2014

01.03.2014 | Research Article

Astrocyte elevated gene-1 is a novel biomarker of epithelial–mesenchymal transition and progression of hepatocellular carcinoma in two China regions

verfasst von: Jiasheng Zheng, Cong Li, Xia Wu, Yingzhuo Yang, Meijun Hao, Shoupeng Sheng, Yu Sun, Honghai Zhang, Jiang Long, Caixia Hu

Erschienen in: Tumor Biology | Ausgabe 3/2014

Einloggen, um Zugang zu erhalten

Abstract

Astrocyte elevated gene-1 (AEG-1) is involved in important biological processes including cell invasion, metastasis, and carcinogenesis. However, its clinical significance has remained largely unknown in hepatocellular carcinoma. Here, specimens from 144 patients with hepatocellular carcinomas in Beijing and Heilongjiang regions were investigated by immunohistochemical staining for AEG-1, vimentin, and E-cadherin expressions. A clinicopathological study revealed that AEG-1 expression level in tumor cells was significantly correlated with TNM stage (P = 0.001) and Edmonson grade (P < 0.0001). In addition, AEG-1, vimentin, and E-cadherin (epithelial–mesenchymal transition (EMT) biomarker) expressions were correlated with each other. These findings suggest that AEG-1 may be an epithelial–mesenchymal transition-associated biomarker in human hepatocellular carcinoma and play important roles in the progression of hepatocellular carcinoma. In addition, the AEG-1 gene is a potential target for elimination of hepatocellular carcinoma in the future.
Literatur
1.
2.
Zurück zum Zitat Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013;47(Suppl):S2–6.PubMedCrossRef Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013;47(Suppl):S2–6.PubMedCrossRef
3.
Zurück zum Zitat Padhya KT, Marrero JA, Singal AG. Recent advances in the treatment of hepatocellular carcinoma. Curr Opin Gastroenterol. 2013;29:285–92.PubMedCrossRef Padhya KT, Marrero JA, Singal AG. Recent advances in the treatment of hepatocellular carcinoma. Curr Opin Gastroenterol. 2013;29:285–92.PubMedCrossRef
4.
Zurück zum Zitat van Zijl F, Zulehner G, Petz M, Schneller D, Kornauth C, Hau M, et al. Epithelial–mesenchymal transition in hepatocellular carcinoma. Future Oncol. 2009;5:1169–79.PubMedCrossRef van Zijl F, Zulehner G, Petz M, Schneller D, Kornauth C, Hau M, et al. Epithelial–mesenchymal transition in hepatocellular carcinoma. Future Oncol. 2009;5:1169–79.PubMedCrossRef
5.
Zurück zum Zitat Lee TK, Poon RT, Yuen AP, et al. Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial–mesenchymal transition. Clin Cancer Res. 2006;12:5369–76.PubMedCrossRef Lee TK, Poon RT, Yuen AP, et al. Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial–mesenchymal transition. Clin Cancer Res. 2006;12:5369–76.PubMedCrossRef
6.
Zurück zum Zitat Su ZZ, Kang DC, Chen Y, et al. Identification and cloning of human astrocyte genes displaying elevated expression after infection with HIV-1 or exposure to HIV-1 envelope glycoprotein by rapid subtraction hybridization, RasH. Oncogene. 2002;21:3592–602.PubMedCrossRef Su ZZ, Kang DC, Chen Y, et al. Identification and cloning of human astrocyte genes displaying elevated expression after infection with HIV-1 or exposure to HIV-1 envelope glycoprotein by rapid subtraction hybridization, RasH. Oncogene. 2002;21:3592–602.PubMedCrossRef
7.
Zurück zum Zitat Kang DC, Su ZZ, Sarkar D, et al. Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1. Gene. 2005;353:8–15.PubMedCrossRef Kang DC, Su ZZ, Sarkar D, et al. Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1. Gene. 2005;353:8–15.PubMedCrossRef
8.
Zurück zum Zitat Brown DM, Ruoslahti E. Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell. 2004;5:365–74.PubMedCrossRef Brown DM, Ruoslahti E. Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell. 2004;5:365–74.PubMedCrossRef
9.
Zurück zum Zitat Meng X, Zhu D, Yang S, et al. Cytoplasmic metadherin (MTDH) provides survival advantage under conditions of stress by acting as RNA-binding protein. J Biol Chem. 2012;287:4485–91.PubMedCentralPubMedCrossRef Meng X, Zhu D, Yang S, et al. Cytoplasmic metadherin (MTDH) provides survival advantage under conditions of stress by acting as RNA-binding protein. J Biol Chem. 2012;287:4485–91.PubMedCentralPubMedCrossRef
10.
Zurück zum Zitat Thirkettle HJ, Mills IG, Whitaker HC, et al. Nuclear LYRIC/AEG-1 interacts with PLZF and relieves PLZF-mediated repression. Oncogene. 2009;28:3663–70.PubMedCrossRef Thirkettle HJ, Mills IG, Whitaker HC, et al. Nuclear LYRIC/AEG-1 interacts with PLZF and relieves PLZF-mediated repression. Oncogene. 2009;28:3663–70.PubMedCrossRef
11.
Zurück zum Zitat Yoo BK, Emdad L, Sarkar D, et al. Astrocyte elevated gene-1 (AEG-1): a multifunctional regulator of normal and abnormal physiology. Pharmacol Ther. 2011;130:1–8.PubMedCentralPubMedCrossRef Yoo BK, Emdad L, Sarkar D, et al. Astrocyte elevated gene-1 (AEG-1): a multifunctional regulator of normal and abnormal physiology. Pharmacol Ther. 2011;130:1–8.PubMedCentralPubMedCrossRef
12.
Zurück zum Zitat Emdad L, Lee SG, Fisher PB, et al. Astrocyte elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis. Proc Natl Acad Sci U S A. 2009;106:21300–5.PubMedCentralPubMedCrossRef Emdad L, Lee SG, Fisher PB, et al. Astrocyte elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis. Proc Natl Acad Sci U S A. 2009;106:21300–5.PubMedCentralPubMedCrossRef
13.
Zurück zum Zitat Lee HJ, Jung DB, Kim SH, et al. Inhibition of hypoxia inducible factor alpha and astrocyte-elevated gene-1 mediates cryptotanshinone exerted antitumor activity in hypoxic PC-3 cells. Evid Based Complement Alternat Med. 2012;2012:1–13. Lee HJ, Jung DB, Kim SH, et al. Inhibition of hypoxia inducible factor alpha and astrocyte-elevated gene-1 mediates cryptotanshinone exerted antitumor activity in hypoxic PC-3 cells. Evid Based Complement Alternat Med. 2012;2012:1–13.
14.
Zurück zum Zitat Noch E, Bookland M, Khalili K. Astrocyte-elevated gene-1 (AEG-1) induction by hypoxia and glucose deprivation in glioblastoma. Cancer Biol Ther. 2011;11:32–9.PubMedCentralPubMedCrossRef Noch E, Bookland M, Khalili K. Astrocyte-elevated gene-1 (AEG-1) induction by hypoxia and glucose deprivation in glioblastoma. Cancer Biol Ther. 2011;11:32–9.PubMedCentralPubMedCrossRef
15.
Zurück zum Zitat Li C, Song H, Geng J, et al. Significance of AEG-1 expression in correlation with VEGF, microvessel density and clinicopathological characteristics in triple-negative breast cancer. J Surg Oncol. 2011;103:184–92.PubMedCrossRef Li C, Song H, Geng J, et al. Significance of AEG-1 expression in correlation with VEGF, microvessel density and clinicopathological characteristics in triple-negative breast cancer. J Surg Oncol. 2011;103:184–92.PubMedCrossRef
16.
Zurück zum Zitat Li C, Song H, Geng J, et al. AEG-1 overexpression: a novel indicator for peritoneal dissemination and lymph node metastasis in epithelial ovarian cancers. Int J Gynecol Cancer. 2011;21:602–8.PubMedCrossRef Li C, Song H, Geng J, et al. AEG-1 overexpression: a novel indicator for peritoneal dissemination and lymph node metastasis in epithelial ovarian cancers. Int J Gynecol Cancer. 2011;21:602–8.PubMedCrossRef
17.
Zurück zum Zitat Li C, Song H, Geng J, et al. Elevated expression of AEG-1 is correlated with cisplatin-based chemoresistance and shortened outcome in patients with stages III–IV serous ovarian carcinoma. Histopathology. 2012;60:953–63.PubMedCrossRef Li C, Song H, Geng J, et al. Elevated expression of AEG-1 is correlated with cisplatin-based chemoresistance and shortened outcome in patients with stages III–IV serous ovarian carcinoma. Histopathology. 2012;60:953–63.PubMedCrossRef
18.
Zurück zum Zitat Song H, Li C, Geng J, et al. Prognostic significance of expression in colorectal carcinoma. Int J Colorectal Dis. 2010;25:1201–9.PubMedCrossRef Song H, Li C, Geng J, et al. Prognostic significance of expression in colorectal carcinoma. Int J Colorectal Dis. 2010;25:1201–9.PubMedCrossRef
19.
Zurück zum Zitat Erdem H, Yildirim U, Uzunlar AK, et al. Relationship among expression of basic-fibroblast growth factor, MTDH/astrocyte elevated gene-1, adenomatous polyposis coli, matrix metalloproteinase 9, and COX-2 markers with prognostic factors in prostate carcinomas. Niger J Clin Pract. 2013;16:418–23.PubMedCrossRef Erdem H, Yildirim U, Uzunlar AK, et al. Relationship among expression of basic-fibroblast growth factor, MTDH/astrocyte elevated gene-1, adenomatous polyposis coli, matrix metalloproteinase 9, and COX-2 markers with prognostic factors in prostate carcinomas. Niger J Clin Pract. 2013;16:418–23.PubMedCrossRef
20.
Zurück zum Zitat Huang W, Yang L, Liang S, et al. AEG-1 is a target of perifosine and is over-expressed in gastric dysplasia and cancers. Dig Dis Sci. 2013;58:2873–80.PubMedCrossRef Huang W, Yang L, Liang S, et al. AEG-1 is a target of perifosine and is over-expressed in gastric dysplasia and cancers. Dig Dis Sci. 2013;58:2873–80.PubMedCrossRef
21.
Zurück zum Zitat Noch EK, Khalili K. The role of AEG-1/MTDH/LYRIC in the pathogenesis of central nervous system disease. Adv Cancer Res. 2013;120:159–92.PubMedCrossRef Noch EK, Khalili K. The role of AEG-1/MTDH/LYRIC in the pathogenesis of central nervous system disease. Adv Cancer Res. 2013;120:159–92.PubMedCrossRef
22.
Zurück zum Zitat Srivastava J, Siddiq A, Emdad L, et al. Astrocyte elevated gene-1 promotes hepatocarcinogenesis: novel insights from a mouse model. Hepatology. 2012;56:1782–91.PubMedCentralPubMedCrossRef Srivastava J, Siddiq A, Emdad L, et al. Astrocyte elevated gene-1 promotes hepatocarcinogenesis: novel insights from a mouse model. Hepatology. 2012;56:1782–91.PubMedCentralPubMedCrossRef
23.
Zurück zum Zitat Wan L, Kang Y. Pleiotropic roles of AEG-1/MTDH/LYRIC in breast cancer. Adv Cancer Res. 2013;120:113–34.PubMedCrossRef Wan L, Kang Y. Pleiotropic roles of AEG-1/MTDH/LYRIC in breast cancer. Adv Cancer Res. 2013;120:113–34.PubMedCrossRef
24.
Zurück zum Zitat Emdad L, Das SK, Dasgupta S, et al. AEG-1/MTDH/LYRIC: signaling pathways, downstream genes, interacting proteins, and regulation of tumor angiogenesis. Adv Cancer Res. 2013;120:75–111.PubMedCentralPubMedCrossRef Emdad L, Das SK, Dasgupta S, et al. AEG-1/MTDH/LYRIC: signaling pathways, downstream genes, interacting proteins, and regulation of tumor angiogenesis. Adv Cancer Res. 2013;120:75–111.PubMedCentralPubMedCrossRef
26.
Zurück zum Zitat Liu K, Guo L, Miao L, et al. Ursolic acid inhibits epithelial–mesenchymal transition by suppressing the expression of astrocyte-elevated gene-1 in human nonsmall cell lung cancer A549 cells. Anticancer Drugs. 2013;24(5):494–503.PubMedCrossRef Liu K, Guo L, Miao L, et al. Ursolic acid inhibits epithelial–mesenchymal transition by suppressing the expression of astrocyte-elevated gene-1 in human nonsmall cell lung cancer A549 cells. Anticancer Drugs. 2013;24(5):494–503.PubMedCrossRef
27.
Zurück zum Zitat He XX, Chang Y, Meng FY, et al. MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo. Oncogene. 2012;31:3357–69.PubMedCrossRef He XX, Chang Y, Meng FY, et al. MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo. Oncogene. 2012;31:3357–69.PubMedCrossRef
28.
Zurück zum Zitat Zhu K, Dai Z, Pan Q, et al. Metadherin promotes hepatocellular carcinoma metastasis through induction of epithelial–mesenchymal transition. Clin Cancer Res. 2011;17:7294–302.PubMedCrossRef Zhu K, Dai Z, Pan Q, et al. Metadherin promotes hepatocellular carcinoma metastasis through induction of epithelial–mesenchymal transition. Clin Cancer Res. 2011;17:7294–302.PubMedCrossRef
29.
Zurück zum Zitat Li X, Kong X, Huo Q, et al. Metadherin enhances the invasiveness of breast cancer cells by inducing epithelial to mesenchymal transition. Cancer Sci. 2011;102:1151–7.PubMedCrossRef Li X, Kong X, Huo Q, et al. Metadherin enhances the invasiveness of breast cancer cells by inducing epithelial to mesenchymal transition. Cancer Sci. 2011;102:1151–7.PubMedCrossRef
30.
Zurück zum Zitat Wei J, Li Z, Chen W, et al. AEG-1 participates in TGF-beta1-induced EMT through p38 MAPK activation. Cell Biol Int. 2013;37:1016–21.PubMedCrossRef Wei J, Li Z, Chen W, et al. AEG-1 participates in TGF-beta1-induced EMT through p38 MAPK activation. Cell Biol Int. 2013;37:1016–21.PubMedCrossRef
31.
Zurück zum Zitat Kohles N, Nagel D, Jüngst D, Stieber P, Holdenrieder S. Predictive value of immunogenic cell death biomarkers HMGB1, sRAGE, and DNase in liver cancer patients receiving transarterial chemoembolization therapy. Tumour Biol. 2012;33:2401–9.PubMedCrossRef Kohles N, Nagel D, Jüngst D, Stieber P, Holdenrieder S. Predictive value of immunogenic cell death biomarkers HMGB1, sRAGE, and DNase in liver cancer patients receiving transarterial chemoembolization therapy. Tumour Biol. 2012;33:2401–9.PubMedCrossRef
32.
Zurück zum Zitat Yao N, Yao D, Wang L, et al. Inhibition of autocrine IGF-II on effect of human HepG2 cell proliferation and angiogenesis factor expression. Tumor Biol. 2012;33:1767–76.CrossRef Yao N, Yao D, Wang L, et al. Inhibition of autocrine IGF-II on effect of human HepG2 cell proliferation and angiogenesis factor expression. Tumor Biol. 2012;33:1767–76.CrossRef
33.
Zurück zum Zitat Sun Y, Sun T, Li C, et al. A polysaccharide from the fungi of Huaier exhibits anti-tumor potential and immunomodulatory effects. Carbohydr Polym. 2013;92:577–82.PubMedCrossRef Sun Y, Sun T, Li C, et al. A polysaccharide from the fungi of Huaier exhibits anti-tumor potential and immunomodulatory effects. Carbohydr Polym. 2013;92:577–82.PubMedCrossRef
Metadaten
Titel
Astrocyte elevated gene-1 is a novel biomarker of epithelial–mesenchymal transition and progression of hepatocellular carcinoma in two China regions
verfasst von
Jiasheng Zheng
Cong Li
Xia Wu
Yingzhuo Yang
Meijun Hao
Shoupeng Sheng
Yu Sun
Honghai Zhang
Jiang Long
Caixia Hu
Publikationsdatum
01.03.2014
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 3/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1300-3

Weitere Artikel der Ausgabe 3/2014

Tumor Biology 3/2014 Zur Ausgabe

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

ASS schützt nicht vor Brustkrebsrezidiven

02.05.2024 Mammakarzinom Nachrichten

Nützt nichts und ist vielleicht sogar schädlich: In einer Phase-3-Studie konnten täglich 300 mg ASS keine Brustkrebsrezidive bei Frauen vermeiden, die ein hohes Risiko für eine Tumorrückkehr aufwiesen. Tendenziell traten unter ASS sogar häufiger Rezidive auf als unter Placebo.

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

30.04.2024 Künstliche Intelligenz Nachrichten

Krebserkrankungen unbekannten Ursprungs (CUP) sind eine diagnostische Herausforderung. KI-Systeme können Pathologen dabei unterstützen, zytologische Bilder zu interpretieren, um den Primärtumor zu lokalisieren.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Update Onkologie

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