Skip to main content
Top
Published in: Medical Oncology 3/2012

01-09-2012 | Original Paper

Decreased expression of ALDH1L1 is associated with a poor prognosis in hepatocellular carcinoma

Authors: Xiao-Qian Chen, Juan-Ru He, Hui-Yun Wang

Published in: Medical Oncology | Issue 3/2012

Login to get access

Abstract

Microarray data suggested that the expression of aldehyde dehydrogenase 1 family member L1 (ALDH1L1) is reduced in hepatocellular carcinoma (HCC). However, the role of ALDH1L1 in HCC carcinogenesis has not been elucidated. In the present study, we investigated the expression of ALDH1L1 in HCC and evaluated its relationship with clinical features and prognosis of HCC patients. Total 112 tumor samples were collected from patients with HCC, who underwent radical hepatectomy. Out of the 112 samples, 16 paired HCC tumorous and corresponding adjacent nontumor tissues were analyzed by real-time quantitative RT-PCR (qRT-PCR) and Western blotting, and the other 96 HCC samples were detected by immunohistochemical method. The qRT-PCR assay showed that the mRNA level of ALDH1L1 was significantly reduced in tumorous tissues compared with the adjacent nontumorous tissues (P = 0.0007), and Western blotting indicated that protein level of ALDH1L1 also notably down-regulated in tumor tissues. Immunohistochemistry detection revealed that decreased ALDH1L1 expression was present in 56.3% (54/96) of HCC patients. Correlation analysis showed that ALDH1L1 expression was significantly correlated with histological differentiation (P = 0.001), HBsAg status (P = 0.024) and serum AFP (P = 0.001). Patients with low expression of ALDH1L1 had poorer prognosis than those with high expression (P = 0.008). Multivariate analysis showed that ALDH1L1 expression was an independent predictor of overall survival (HR, 0.349; 95% CI, 0.157–0.774; P = 0.01). The results in this study, for the first time, reveal that the mRNA and protein expressions of ALDH1L1 are significantly reduced in HCC tissues and its low protein expression is a new and potential prognostic marker for the survival of HCC patients.
Literature
1.
go back to reference Bruix J, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European association for the study of the liver. J Hepatol. 2001;35(3):421–30.PubMedCrossRef Bruix J, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European association for the study of the liver. J Hepatol. 2001;35(3):421–30.PubMedCrossRef
2.
go back to reference He J, et al. Major causes of death among men and women in China. N Engl J Med. 2005;353(11):1124–34.PubMedCrossRef He J, et al. Major causes of death among men and women in China. N Engl J Med. 2005;353(11):1124–34.PubMedCrossRef
3.
go back to reference Seeff LB, Hoofnagle JH. Epidemiology of hepatocellular carcinoma in areas of low hepatitis B and hepatitis C endemicity. Oncogene. 2006;25(27):3771–7.PubMedCrossRef Seeff LB, Hoofnagle JH. Epidemiology of hepatocellular carcinoma in areas of low hepatitis B and hepatitis C endemicity. Oncogene. 2006;25(27):3771–7.PubMedCrossRef
4.
go back to reference Feo F, et al. Hepatocellular carcinoma as a complex polygenic disease. Interpretive analysis of recent developments on genetic predisposition. Biochim Biophys Acta. 2006;1765(2):126–47.PubMed Feo F, et al. Hepatocellular carcinoma as a complex polygenic disease. Interpretive analysis of recent developments on genetic predisposition. Biochim Biophys Acta. 2006;1765(2):126–47.PubMed
5.
go back to reference Kwon OS, et al. Effect of alcohol on the development of hepatocellular carcinoma in patients with hepatitis B virus-related cirrhosis: a cross-sectional case-control study. Korean J Hepatol. 2010;16(3):308–14.PubMedCrossRef Kwon OS, et al. Effect of alcohol on the development of hepatocellular carcinoma in patients with hepatitis B virus-related cirrhosis: a cross-sectional case-control study. Korean J Hepatol. 2010;16(3):308–14.PubMedCrossRef
6.
go back to reference Chen Ban K, et al. Comparison of the expression of beta-catenin in hepatocellular carcinoma in areas with high and low levels of exposure to aflatoxin B1. J Surg Oncol. 2004;86(3):157–63.PubMedCrossRef Chen Ban K, et al. Comparison of the expression of beta-catenin in hepatocellular carcinoma in areas with high and low levels of exposure to aflatoxin B1. J Surg Oncol. 2004;86(3):157–63.PubMedCrossRef
7.
go back to reference Bosch FX, Ribes J, Borras J. Epidemiology of primary liver cancer. Semin Liver Dis. 1999;19(3):271–85.PubMedCrossRef Bosch FX, Ribes J, Borras J. Epidemiology of primary liver cancer. Semin Liver Dis. 1999;19(3):271–85.PubMedCrossRef
8.
go back to reference Krupenko SA. FDH: an aldehyde dehydrogenase fusion enzyme in folate metabolism. Chem Biol Interact. 2009;178(1–3):84–93.PubMedCrossRef Krupenko SA. FDH: an aldehyde dehydrogenase fusion enzyme in folate metabolism. Chem Biol Interact. 2009;178(1–3):84–93.PubMedCrossRef
9.
go back to reference Krupenko SA, Oleinik NV. 10-formyltetrahydrofolate dehydrogenase one of the major folate enzymes, is down-regulated in tumor tissues and possesses suppressor effects on cancer cells. Cell Growth Differ. 2002;13(5):227–36.PubMed Krupenko SA, Oleinik NV. 10-formyltetrahydrofolate dehydrogenase one of the major folate enzymes, is down-regulated in tumor tissues and possesses suppressor effects on cancer cells. Cell Growth Differ. 2002;13(5):227–36.PubMed
10.
go back to reference Krebs HA, Hems R, Tyler B. The regulation of folate and methionine metabolism. Biochem J. 1976;158(2):341–53.PubMed Krebs HA, Hems R, Tyler B. The regulation of folate and methionine metabolism. Biochem J. 1976;158(2):341–53.PubMed
11.
go back to reference Kim DW, et al. Properties of tetrahydropteroylpentaglutamate bound to 10-formyltetrahydrofolate dehydrogenase. Biochemistry. 1996;35(49):15772–83.PubMedCrossRef Kim DW, et al. Properties of tetrahydropteroylpentaglutamate bound to 10-formyltetrahydrofolate dehydrogenase. Biochemistry. 1996;35(49):15772–83.PubMedCrossRef
12.
go back to reference Wagner C, et al. 10-Formyltetrahydrofolate dehydrogenase: identification of the natural folate ligand, covalent labeling, and partial tryptic digestion. Arch Biochem Biophys. 1995;316(1):141–7.PubMedCrossRef Wagner C, et al. 10-Formyltetrahydrofolate dehydrogenase: identification of the natural folate ligand, covalent labeling, and partial tryptic digestion. Arch Biochem Biophys. 1995;316(1):141–7.PubMedCrossRef
13.
go back to reference Oleinik NV, Krupenko SA. Ectopic expression of 10-formyltetrahydrofolate dehydrogenase in A549 cells induces G1 cell cycle arrest and apoptosis. Mol Cancer Res. 2003;1(8):577–88.PubMed Oleinik NV, Krupenko SA. Ectopic expression of 10-formyltetrahydrofolate dehydrogenase in A549 cells induces G1 cell cycle arrest and apoptosis. Mol Cancer Res. 2003;1(8):577–88.PubMed
14.
go back to reference Oleinik NV, Krupenko NI, Krupenko SA. ALDH1L1 inhibits cell motility via dephosphorylation of cofilin by PP1 and PP2A. Oncogene. 2010;29(47):6233–44.PubMedCrossRef Oleinik NV, Krupenko NI, Krupenko SA. ALDH1L1 inhibits cell motility via dephosphorylation of cofilin by PP1 and PP2A. Oncogene. 2010;29(47):6233–44.PubMedCrossRef
15.
go back to reference Tackels-Horne D, et al. Identification of differentially expressed genes in hepatocellular carcinoma and metastatic liver tumors by oligonucleotide expression profiling. Cancer. 2001;92(2):395–405.PubMedCrossRef Tackels-Horne D, et al. Identification of differentially expressed genes in hepatocellular carcinoma and metastatic liver tumors by oligonucleotide expression profiling. Cancer. 2001;92(2):395–405.PubMedCrossRef
16.
go back to reference Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101–8.PubMedCrossRef Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101–8.PubMedCrossRef
17.
go back to reference Bailey LB, Gregory JF 3rd. Folate metabolism and requirements. J Nutr. 1999;129(4):779–82.PubMed Bailey LB, Gregory JF 3rd. Folate metabolism and requirements. J Nutr. 1999;129(4):779–82.PubMed
18.
go back to reference Benkovic SJ. The transformylase enzymes in de novo purine biosynthesis. Trends Biochem Sci. 1984;9:320–2.CrossRef Benkovic SJ. The transformylase enzymes in de novo purine biosynthesis. Trends Biochem Sci. 1984;9:320–2.CrossRef
19.
go back to reference Jhaveri MS, Wagner C, Trepel JB. Impact of extracellular folate levels on global gene expression. Mol Pharmacol. 2001;60(6):1288–95.PubMed Jhaveri MS, Wagner C, Trepel JB. Impact of extracellular folate levels on global gene expression. Mol Pharmacol. 2001;60(6):1288–95.PubMed
20.
go back to reference Kruman II, et al. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer’s disease. J Neurosci. 2002;22(5):1752–62.PubMed Kruman II, et al. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer’s disease. J Neurosci. 2002;22(5):1752–62.PubMed
21.
go back to reference Huang RF, et al. Folate deficiency induces a cell cycle-specific apoptosis in HepG2 cells. J Nutr. 1999;129(1):25–31.PubMed Huang RF, et al. Folate deficiency induces a cell cycle-specific apoptosis in HepG2 cells. J Nutr. 1999;129(1):25–31.PubMed
22.
go back to reference Rodriguez FJ, et al. Gene expression profiling of NF-1-associated and sporadic pilocytic astrocytoma identifies aldehyde dehydrogenase 1 family member L1 (ALDH1L1) as an underexpressed candidate biomarker in aggressive subtypes. J Neuropathol Exp Neurol. 2008;67(12):1194–204.PubMedCrossRef Rodriguez FJ, et al. Gene expression profiling of NF-1-associated and sporadic pilocytic astrocytoma identifies aldehyde dehydrogenase 1 family member L1 (ALDH1L1) as an underexpressed candidate biomarker in aggressive subtypes. J Neuropathol Exp Neurol. 2008;67(12):1194–204.PubMedCrossRef
23.
go back to reference Oleinik NV, et al. Cancer cells activate p53 in response to 10-formyltetrahydrofolate dehydrogenase expression. Biochem J. 2005;391(Pt 3):503–11.PubMed Oleinik NV, et al. Cancer cells activate p53 in response to 10-formyltetrahydrofolate dehydrogenase expression. Biochem J. 2005;391(Pt 3):503–11.PubMed
24.
go back to reference Oleinik NV, Krupenko NI, Krupenko SA. Cooperation between JNK1 and JNK2 in activation of p53 apoptotic pathway. Oncogene. 2007;26(51):7222–30.PubMedCrossRef Oleinik NV, Krupenko NI, Krupenko SA. Cooperation between JNK1 and JNK2 in activation of p53 apoptotic pathway. Oncogene. 2007;26(51):7222–30.PubMedCrossRef
25.
go back to reference Ghose S, et al. 10-formyltetrahydrofolate dehydrogenase-induced c-Jun-NH2-kinase pathways diverge at the c-Jun-NH2-kinase substrate level in cells with different p53 status. Mol Cancer Res. 2009;7(1):99–107.PubMedCrossRef Ghose S, et al. 10-formyltetrahydrofolate dehydrogenase-induced c-Jun-NH2-kinase pathways diverge at the c-Jun-NH2-kinase substrate level in cells with different p53 status. Mol Cancer Res. 2009;7(1):99–107.PubMedCrossRef
Metadata
Title
Decreased expression of ALDH1L1 is associated with a poor prognosis in hepatocellular carcinoma
Authors
Xiao-Qian Chen
Juan-Ru He
Hui-Yun Wang
Publication date
01-09-2012
Publisher
Springer US
Published in
Medical Oncology / Issue 3/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-011-0075-x

Other articles of this Issue 3/2012

Medical Oncology 3/2012 Go to the issue