title: Identification of ADH4 as a novel and potential prognostic marker in hepatocellular carcinoma.
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.
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Room 617, Guangzhou, 510060, Guangdong, China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Wei
authors.forename: Mei-Yin
authors.initials: MY
authors.lastname: Zhang
authors.forename: Hui-Lan
authors.initials: HL
authors.lastname: Rao
authors.forename: Heng-Ying
authors.initials: HY
authors.lastname: Pu
authors.forename: Hui-Zhong
authors.initials: HZ
authors.lastname: Zhang
authors.forename: Hui-Yun
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000401:mortality*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000201:enzymology / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D015415:Biomarkers; D000426:Alcohol Dehydrogenase; C105552:alcohol dehydrogenase IV