| Metabolism of alcohol in the liver includes three steps of main process:the first step is from ethanol to acetaldehyde under the action of oxidation of alcohol dehydrogenase (ADH); the second step is from acetaldehyde to acetic acid under the action of oxidation of aldehyde dehydrogenase (ALDH); the third step is acetic acid decomposed into fatty acids, cholesterol and ketone bodies. The metabolism of alcohol is related to the occurrence and development of liver cancer. Ethanol is mainly metabolized in the liver by ADHs and ALDHs enzymes, which are encoded by ADHs and ALDHs. Changes in these genes have been associated with the risk of human malignancies including primary liver cancer (PLC). However, the role of those genes in PLC patients’outcome is not largely known.ObjectivesThe objective of the study is to detect the expression levels of ADH and ALDH genes, and analyze the association of the expression levels of ADH and ALDH genes and the prognosis of PLC patients after surgery.Methods1. The tumor tissues and adjacent tumor tissues of 85 male patients with liver cancer were collected, and their clinical data before surgery were also collected. Then we followed up their postoperative information.2. The expression of ADH1 and ALDH2 were detected by quantitative real-time PCR in paired tumor and adjacent tumor tissue from 85 male PLC patients.3. Statistical analysis:Comparisons of the mRNA expression levels between tumor derived tissues and the adjacent non-tumor derived tissues were conducted using Wilcoxon tests. Comparisons of the mRNA expression between alcohol consumers and non-drinkers were conducted using Mann-Whitney tests. Correlations between different gene expression data were conducted using Spearman rank correlation analysis. Overall survival (OS) curves and recurrence-free survival (RFS) curves of different groups were generated using the Kaplan-Meier method. Differences amongst these curves were analyzed using the Log-rank analysis. Independent prognostic factors associated with survival and non-recurrence time after surgery in male PLC patients were analyzed using Cox proportional hazard model.Results1. The ADH1 and ALDH2 mRNA levels were significantly lower in tumor tissues compared to that in the adjacent tumor tissues (P<O.001), and the expression of ADH1 and ALDH2 genes showed a positive correlation.2. Kaplan-Meier survival analysis showed that patients with a low ratio of ADH1B or ALDH2 expression in tumor vs. non-tumor tissue had a poor RFS (P=0.002, P=0.007), for ADH1B, lower expression ratio was also associated poor OS (P=0.017). Similarly, significant poor OS was found among patients with lower expression in either tumor or non-tumor tissues of ADH1A (P=0.026, P=0.003) and/or ALDH2 expression (P=0.044, P=0.010) respectively. Cox proportional hazard model for multivariate analysis showed that the ratio of ADH1B expression level in tumor vs. non-tumor was an independent prognostic factor for non-recurrence time after surgery in PLC patients, and also ADH1A expression level in non-tumor tissue was an independent prognostic indicator for survival time in PLC patients with postoperative.Conclusions1. In male PLC patients, the expression levels of ADH1 and ALDH2 in tumor tissues were significantly lower than adjacent tumor tissues. The expression levels of ADH1 and ALDH2 were significant positive correlation.2. When the ratio of ADH1B expression level in tumor vs. non-tumor was low, the male PLC patients had a short RFS time after surgery, and when ADH1A expression level in non-tumor tissue was low, the male PLC patients had a short OS time after surgery. |
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