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Erschienen in: Medical Oncology 11/2014

01.11.2014 | Original Paper

High ATF5 expression is a favorable prognostic indicator in patients with hepatocellular carcinoma after hepatectomy

verfasst von: Yujing Wu, Binbin Wu, Renpin Chen, Yongke Zheng, Zhiming Huang

Erschienen in: Medical Oncology | Ausgabe 11/2014

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Abstract

Activating transcription factor 5 (ATF5) is a member of the ATF/CREB family involved in diverse physiological functions, ranging from metabolite homeostasis to cellular differentiations and regulation of the cell cycle. However, the clinical significance of ATF5 expression in patients with hepatocellular carcinoma (HCC) is unknown. We investigated ATF5 mRNA expression in tumors and adjacent non-tumor hepatic tissues from 119 HCC patients using quantitative real-time PCR. Association between the ATF5 mRNA expression level and clinical and pathological parameters, including recurrence-free survival (RFS) and overall survival, were also evaluated using appropriate statistical methods. ATF5 was downregulated significantly (P < 0.001) in the tumor versus matched HCC non-tumor hepatic tissue, with average mRNA expression levels of 0.25 ± 0.92 and 0.41 ± 1.19, respectively. Low ATF5 expression was correlated significantly with liver cirrhosis, intrahepatic metastasis, and TNM stage (P < 0.05). Additionally, both Kaplan–Meier survival curve and multivariate analyses showed a relationship between ATF5 and RFS. In conclusion, a low expression level of ATF5 in HCC indicated aggressive tumor behavior and predicted a worse clinical outcome. ATF5 may be useful as a novel prognostic indicator in hepatocellular carcinoma.
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Literatur
3.
Zurück zum Zitat Zhu AX. Hepatocellular carcinoma: are we making progress? Cancer Invest. 2003;21(3):418–28.PubMedCrossRef Zhu AX. Hepatocellular carcinoma: are we making progress? Cancer Invest. 2003;21(3):418–28.PubMedCrossRef
4.
Zurück zum Zitat El-Serag HB. Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol. 2002;35(5 Suppl 2):S72–8.PubMedCrossRef El-Serag HB. Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol. 2002;35(5 Suppl 2):S72–8.PubMedCrossRef
6.
Zurück zum Zitat Zhang B, Yang B. Combined alpha fetoprotein testing and ultrasonography as a screening test for primary liver cancer. J Med Screen. 1999;6(2):108–10.PubMedCrossRef Zhang B, Yang B. Combined alpha fetoprotein testing and ultrasonography as a screening test for primary liver cancer. J Med Screen. 1999;6(2):108–10.PubMedCrossRef
7.
Zurück zum Zitat Nakamura S, Nouso K, Sakaguchi K, Ito YM, Ohashi Y, Kobayashi Y, et al. Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size. Am J Gastroenterol. 2006;101(9):2038–43. doi:10.1111/j.1572-0241.2006.00681.x.PubMedCrossRef Nakamura S, Nouso K, Sakaguchi K, Ito YM, Ohashi Y, Kobayashi Y, et al. Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size. Am J Gastroenterol. 2006;101(9):2038–43. doi:10.​1111/​j.​1572-0241.​2006.​00681.​x.PubMedCrossRef
11.
Zurück zum Zitat Lee HY, Angelastro JM, Kenney AM, Mason CA, Greene LA. Reciprocal actions of ATF5 and Shh in proliferation of cerebellar granule neuron progenitor cells. Dev Neurobiol. 2012;72(6):789–804. doi:10.1002/dneu.20979.PubMedCrossRef Lee HY, Angelastro JM, Kenney AM, Mason CA, Greene LA. Reciprocal actions of ATF5 and Shh in proliferation of cerebellar granule neuron progenitor cells. Dev Neurobiol. 2012;72(6):789–804. doi:10.​1002/​dneu.​20979.PubMedCrossRef
13.
Zurück zum Zitat Chen A, Qian D, Wang B, Hu M, Lu J, Qi Y, et al. ATF5 is overexpressed in epithelial ovarian carcinomas and interference with its function increases apoptosis through the downregulation of Bcl-2 in SKOV-3 cells. Int J Gynecol Pathol. 2012;31(6):532–7. doi:10.1097/PGP.0b013e31824df26b.PubMedCrossRef Chen A, Qian D, Wang B, Hu M, Lu J, Qi Y, et al. ATF5 is overexpressed in epithelial ovarian carcinomas and interference with its function increases apoptosis through the downregulation of Bcl-2 in SKOV-3 cells. Int J Gynecol Pathol. 2012;31(6):532–7. doi:10.​1097/​PGP.​0b013e31824df26b​.PubMedCrossRef
15.
19.
Zurück zum Zitat Berger AJ, Kluger HM, Li N, Kielhorn E, Halaban R, Ronai Z, et al. Subcellular localization of activating transcription factor 2 in melanoma specimens predicts patient survival. Cancer Res. 2003;63(23):8103–7.PubMed Berger AJ, Kluger HM, Li N, Kielhorn E, Halaban R, Ronai Z, et al. Subcellular localization of activating transcription factor 2 in melanoma specimens predicts patient survival. Cancer Res. 2003;63(23):8103–7.PubMed
21.
Zurück zum Zitat Persengiev SP, Green MR. The role of ATF/CREB family members in cell growth, survival and apoptosis. Apoptosis Int J Program Cell Death. 2003;8(3):225–8.CrossRef Persengiev SP, Green MR. The role of ATF/CREB family members in cell growth, survival and apoptosis. Apoptosis Int J Program Cell Death. 2003;8(3):225–8.CrossRef
22.
Zurück zum Zitat Angelastro JM, Canoll PD, Kuo J, Weicker M, Costa A, Bruce JN, et al. Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5. Oncogene. 2006;25(6):907–16. doi:10.1038/sj.onc.1209116.PubMedCrossRef Angelastro JM, Canoll PD, Kuo J, Weicker M, Costa A, Bruce JN, et al. Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5. Oncogene. 2006;25(6):907–16. doi:10.​1038/​sj.​onc.​1209116.PubMedCrossRef
23.
Zurück zum Zitat Sheng Z, Li L, Zhu LJ, Smith TW, Demers A, Ross AH, et al. A genome-wide RNA interference screen reveals an essential CREB3L2-ATF5-MCL1 survival pathway in malignant glioma with therapeutic implications. Nat Med. 2010;16(6):671–7. doi:10.1038/nm.2158.PubMedCrossRefPubMedCentral Sheng Z, Li L, Zhu LJ, Smith TW, Demers A, Ross AH, et al. A genome-wide RNA interference screen reveals an essential CREB3L2-ATF5-MCL1 survival pathway in malignant glioma with therapeutic implications. Nat Med. 2010;16(6):671–7. doi:10.​1038/​nm.​2158.PubMedCrossRefPubMedCentral
24.
Zurück zum Zitat Mittal AK, Hegde GV, Aoun P, Bociek RG, Dave BJ, Joshi AD, et al. Molecular basis of aggressive disease in chronic lymphocytic leukemia patients with 11q deletion and trisomy 12 chromosomal abnormalities. Int J Mol Med. 2007;20(4):461–9.PubMed Mittal AK, Hegde GV, Aoun P, Bociek RG, Dave BJ, Joshi AD, et al. Molecular basis of aggressive disease in chronic lymphocytic leukemia patients with 11q deletion and trisomy 12 chromosomal abnormalities. Int J Mol Med. 2007;20(4):461–9.PubMed
26.
Zurück zum Zitat Monaco SE, Angelastro JM, Szabolcs M, Greene LA. The transcription factor ATF5 is widely expressed in carcinomas, and interference with its function selectively kills neoplastic, but not nontransformed, breast cell lines. Int J Cancer. 2007;120(9):1883–90. doi:10.1002/ijc.22469.PubMedCrossRef Monaco SE, Angelastro JM, Szabolcs M, Greene LA. The transcription factor ATF5 is widely expressed in carcinomas, and interference with its function selectively kills neoplastic, but not nontransformed, breast cell lines. Int J Cancer. 2007;120(9):1883–90. doi:10.​1002/​ijc.​22469.PubMedCrossRef
27.
Zurück zum Zitat Pascual M, Gomez-Lechon MJ, Castell JV, Jover R. ATF5 is a highly abundant liver-enriched transcription factor that cooperates with constitutive androstane receptor in the transactivation of CYP2B6: implications in hepatic stress responses. Drug Metab Dispos. 2008;36(6):1063–72. doi:10.1124/dmd.107.019380.PubMedCrossRef Pascual M, Gomez-Lechon MJ, Castell JV, Jover R. ATF5 is a highly abundant liver-enriched transcription factor that cooperates with constitutive androstane receptor in the transactivation of CYP2B6: implications in hepatic stress responses. Drug Metab Dispos. 2008;36(6):1063–72. doi:10.​1124/​dmd.​107.​019380.PubMedCrossRef
Metadaten
Titel
High ATF5 expression is a favorable prognostic indicator in patients with hepatocellular carcinoma after hepatectomy
verfasst von
Yujing Wu
Binbin Wu
Renpin Chen
Yongke Zheng
Zhiming Huang
Publikationsdatum
01.11.2014
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 11/2014
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0269-0

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