基因多态性、代谢活性以及醇脱氢酶和乙醛脱氢酶含量对肝细胞癌患者预后的影响。
Effects of Gene Polymorphisms, Metabolic Activity, and Content of Alcohol Dehydrogenase and Acetaldehyde Dehydrogenases on Prognosis of Hepatocellular Carcinoma Patients.
机构信息
Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, China.
出版信息
Turk J Gastroenterol. 2022 Jul;33(7):606-614. doi: 10.5152/tjg.2022.21340.
BACKGROUND
Alcohol dehydrogenase and acetaldehyde dehydrogenases have been associated with hepatocellular carcinoma, but how alcohol dehydrogenase and acetaldehyde dehydrogenases alter the prognosis of hepatocellular carcinoma have not been completely elucidated.
METHODS
Metabolic activities, gene polymorphisms, and content of alcohol dehydrogenase and acetaldehyde dehydrogenases were determined in 68 fibrotic livers from hepatocellular carcinoma patients. These characteristics were then correlated with clinical features and prognosis in these patients.
RESULTS
The median survival time of the ALDH-high activity group (727 days) was increased by 128% compared with that of ALDH-low activity group (319 days), and there was a significant negative correlation between the activity of acetaldehyde dehydrogenases and the level of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. There was no difference in survival time between ALDH2-high and ALDH2-low expression group, though the activity of acetaldehyde dehydrogenases had correlation with the content of ALDH2 (r = 0.6887, P < .001). Mutation at ALDH2rs671 significantly decreased both the activity and content of acetalde- hyde dehydrogenases, but the polymorphism had no relationship with progression of hepatocellular carcinoma patients. In addition, the activity and 3 polymorphisms of alcohol dehydrogenase had no effect on overall survival. Mutation at ADH1Crs698 significantly decreased both the activity and content of alcohol dehydrogenase (P < .05), mutation at ADH1C rs2241894 had an inverse effect, and mutation at ADH1B rs1229984 increased activity but did not affect content. The activity of alcohol dehydrogenase had a moderate cor- relation with the content of ADH1A and ADH1C in livers (P < .05).
CONCLUSION
Low activity of acetaldehyde dehydrogenases in livers correlates with poor prognosis and clinical progression in hepatocel- lular carcinoma patients, and both gene polymorphisms and content influence its metabolic activity.
背景
乙醇脱氢酶和乙醛脱氢酶与肝细胞癌有关，但乙醇脱氢酶和乙醛脱氢酶如何改变肝细胞癌的预后尚未完全阐明。
方法
在 68 例肝癌纤维化肝脏中测定了乙醇脱氢酶和乙醛脱氢酶的代谢活性、基因多态性和含量，并将这些特征与这些患者的临床特征和预后相关联。
结果
与乙醛脱氢酶低活性组（319 天）相比，乙醛脱氢酶高活性组（727 天）的中位生存时间延长了 128%，并且乙醛脱氢酶的活性与丙氨酸转氨酶、天冬氨酸转氨酶和碱性磷酸酶的水平呈显著负相关。ALDH2 高表达组和 ALDH2 低表达组的生存时间无差异，尽管乙醛脱氢酶的活性与 ALDH2 的含量相关（r = 0.6887，P <.001）。ALDH2rs671 突变显著降低了乙醛脱氢酶的活性和含量，但多态性与肝细胞癌患者的进展无关。此外，乙醇脱氢酶的活性和 3 种多态性对总生存率均无影响。ADH1Crs698 突变显著降低了乙醇脱氢酶的活性和含量（P <.05），ADH1Crs2241894 突变具有相反的作用，ADH1Brs1229984 突变增加了活性但不影响含量。乙醇脱氢酶的活性与肝脏中 ADH1A 和 ADH1C 的含量呈中度相关（P <.05）。
结论
肝脏中乙醛脱氢酶活性低与肝细胞癌患者的预后不良和临床进展相关，基因多态性和含量均影响其代谢活性。
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