Identification of ADH4 as a novel and potential prognostic marker in hepatocellular carcinoma
Alcohol dehydrogenase 4 (ADH4) is an important member of ADH family that metabolize a wide variety of substrates including ethanol and retinol. Studies demonstrated that ADH4 was involved in cancer. Microarray data showed that the expression of ADH4 was reduced in hepatocellular carcinoma (HCC). How...
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Published in | Medical oncology (Northwood, London, England) Vol. 29; no. 4; pp. 2737 - 2743 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Boston
Springer US
01.12.2012
Springer Nature B.V |
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Abstract | Alcohol dehydrogenase 4 (ADH4) is an important member of ADH family that metabolize a wide variety of substrates including ethanol and retinol. Studies demonstrated that ADH4 was involved in cancer. Microarray data showed that the expression of ADH4 was reduced in hepatocellular carcinoma (HCC). However, the role of ADH4 in HCC carcinogenesis remains undefined. The aim of this study is to explore the clinical significance of ADH4 in progression and prognosis of HCC. The expression levels of ADH4 in 15 paired HCC and noncancerous (NC) liver tissues were measured by qRT-PCR and those in 4 paired samples by Western blotting. Another 91 paraffin-embedded HCC tissues were examined by immunohistochemistry. The qRT-PCR result showed that the expression level of ADH4 mRNA in HCC was significantly lower than that in NC tissues (
P
< 0.0001). Western blotting also displayed that ADH4 protein was notably reduced in HCC. Immunohistochemistry assay confirmed that ADH4 protein was remarkably reduced in 59.3% HCC. The expression of ADH4 was correlated with the pathology grade (
P
= 0.031) and serum AFP (
P
= 0.022). HCC patients with lower ADH4 expression had much worse overall survival rate than that with high expression (
P
< 0.001). Furthermore, multivariate analysis showed that ADH4 expression was an independent predictor of overall survival (HR, 0.154; 95%CI, 0.044–0.543;
P
= 0.004). This is the first time that the expression levels of ADH4 mRNA and protein have found to be markedly reduced in HCC tissues and significantly associated with survival, suggesting that ADH4 is a novel and potential prognostic marker for HCC patients. |
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AbstractList | Alcohol dehydrogenase 4 (ADH4) is an important member of ADH family that metabolize a wide variety of substrates including ethanol and retinol. Studies demonstrated that ADH4 was involved in cancer. Microarray data showed that the expression of ADH4 was reduced in hepatocellular carcinoma (HCC). However, the role of ADH4 in HCC carcinogenesis remains undefined. The aim of this study is to explore the clinical significance of ADH4 in progression and prognosis of HCC. The expression levels of ADH4 in 15 paired HCC and noncancerous (NC) liver tissues were measured by qRT-PCR and those in 4 paired samples by Western blotting. Another 91 paraffin-embedded HCC tissues were examined by immunohistochemistry. The qRT-PCR result showed that the expression level of ADH4 mRNA in HCC was significantly lower than that in NC tissues (P<0.0001). Western blotting also displayed that ADH4 protein was notably reduced in HCC. Immunohistochemistry assay confirmed that ADH4 protein was remarkably reduced in 59.3% HCC. The expression of ADH4 was correlated with the pathology grade (P=0.031) and serum AFP (P=0.022). HCC patients with lower ADH4 expression had much worse overall survival rate than that with high expression (P<0.001). Furthermore, multivariate analysis showed that ADH4 expression was an independent predictor of overall survival (HR, 0.154; 95%CI, 0.044-0.543; P=0.004). This is the first time that the expression levels of ADH4 mRNA and protein have found to be markedly reduced in HCC tissues and significantly associated with survival, suggesting that ADH4 is a novel and potential prognostic marker for HCC patients. Alcohol dehydrogenase 4 (ADH4) is an important member of ADH family that metabolize a wide variety of substrates including ethanol and retinol. Studies demonstrated that ADH4 was involved in cancer. Microarray data showed that the expression of ADH4 was reduced in hepatocellular carcinoma (HCC). However, the role of ADH4 in HCC carcinogenesis remains undefined. The aim of this study is to explore the clinical significance of ADH4 in progression and prognosis of HCC. The expression levels of ADH4 in 15 paired HCC and noncancerous (NC) liver tissues were measured by qRT-PCR and those in 4 paired samples by Western blotting. Another 91 paraffin-embedded HCC tissues were examined by immunohistochemistry. The qRT-PCR result showed that the expression level of ADH4 mRNA in HCC was significantly lower than that in NC tissues (P < 0.0001). Western blotting also displayed that ADH4 protein was notably reduced in HCC. Immunohistochemistry assay confirmed that ADH4 protein was remarkably reduced in 59.3% HCC. The expression of ADH4 was correlated with the pathology grade (P = 0.031) and serum AFP (P = 0.022). HCC patients with lower ADH4 expression had much worse overall survival rate than that with high expression (P < 0.001). Furthermore, multivariate analysis showed that ADH4 expression was an independent predictor of overall survival (HR, 0.154; 95%CI, 0.044-0.543; P = 0.004). This is the first time that the expression levels of ADH4 mRNA and protein have found to be markedly reduced in HCC tissues and significantly associated with survival, suggesting that ADH4 is a novel and potential prognostic marker for HCC patients.[PUBLICATION ABSTRACT] Alcohol dehydrogenase 4 (ADH4) is an important member of ADH family that metabolize a wide variety of substrates including ethanol and retinol. Studies demonstrated that ADH4 was involved in cancer. Microarray data showed that the expression of ADH4 was reduced in hepatocellular carcinoma (HCC). However, the role of ADH4 in HCC carcinogenesis remains undefined. The aim of this study is to explore the clinical significance of ADH4 in progression and prognosis of HCC. The expression levels of ADH4 in 15 paired HCC and noncancerous (NC) liver tissues were measured by qRT-PCR and those in 4 paired samples by Western blotting. Another 91 paraffin-embedded HCC tissues were examined by immunohistochemistry. The qRT-PCR result showed that the expression level of ADH4 mRNA in HCC was significantly lower than that in NC tissues ( P < 0.0001). Western blotting also displayed that ADH4 protein was notably reduced in HCC. Immunohistochemistry assay confirmed that ADH4 protein was remarkably reduced in 59.3% HCC. The expression of ADH4 was correlated with the pathology grade ( P = 0.031) and serum AFP ( P = 0.022). HCC patients with lower ADH4 expression had much worse overall survival rate than that with high expression ( P < 0.001). Furthermore, multivariate analysis showed that ADH4 expression was an independent predictor of overall survival (HR, 0.154; 95%CI, 0.044–0.543; P = 0.004). This is the first time that the expression levels of ADH4 mRNA and protein have found to be markedly reduced in HCC tissues and significantly associated with survival, suggesting that ADH4 is a novel and potential prognostic marker for HCC patients. |
Author | Rao, Hui-Lan Zhang, Mei-Yin Wei, Rong-Rong Wang, Hui-Yun Pu, Heng-Ying Zhang, Hui-Zhong |
Author_xml | – sequence: 1 givenname: Rong-Rong surname: Wei fullname: Wei, Rong-Rong organization: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University – sequence: 2 givenname: Mei-Yin surname: Zhang fullname: Zhang, Mei-Yin organization: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University – sequence: 3 givenname: Hui-Lan surname: Rao fullname: Rao, Hui-Lan organization: Department of Pathology, Cancer Center, Sun Yat-Sen University – sequence: 4 givenname: Heng-Ying surname: Pu fullname: Pu, Heng-Ying organization: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University – sequence: 5 givenname: Hui-Zhong surname: Zhang fullname: Zhang, Hui-Zhong organization: Department of Pathology, Cancer Center, Sun Yat-Sen University – sequence: 6 givenname: Hui-Yun surname: Wang fullname: Wang, Hui-Yun email: wanghyun@mail.sysu.edu.cn organization: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/22147505$$D View this record in MEDLINE/PubMed |
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Cites_doi | 10.1053/jhep.2002.36780 10.1159/000090173 10.1158/1055-9965.EPI-09-0499 10.1021/bi00321a012 10.1093/aje/155.4.323 10.1002/1097-0142(20010715)92:2<395::AID-CNCR1335>3.0.CO;2-U 10.1038/sj.npp.1300925 10.1002/hep.510270404 10.1002/mc.20714 10.1002/ijc.1440 10.1016/j.biopsych.2006.05.017 10.1176/appi.ajp.162.5.1005 10.1097/01.fpc.0000180141.77036.dc 10.1111/j.1526-4610.2009.01569.x 10.2146/ajhp060647 10.1016/S0014-5793(96)01204-5 10.1111/j.1742-4658.2007.05665.x 10.1016/S0009-2797(02)00225-9 10.1111/j.1369-1600.2010.00236.x |
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Keywords | Immunohistochemistry ADH4 Hepatocellular carcinoma Prognosis |
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SubjectTerms | Adolescent Adult Aged Alcohol Dehydrogenase - analysis Alcohol Dehydrogenase - genetics Alcohol Dehydrogenase - physiology Biomarkers Carcinoma, Hepatocellular - enzymology Carcinoma, Hepatocellular - mortality Female Hematology Humans Immunohistochemistry Internal Medicine Liver Neoplasms - enzymology Liver Neoplasms - mortality Male Medicine Medicine & Public Health Middle Aged Multivariate Analysis Oncology Original Paper Pathology Prognosis Proportional Hazards Models |
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Title | Identification of ADH4 as a novel and potential prognostic marker in hepatocellular carcinoma |
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