Jelski Wojciech, Laniewska-Dunaj Magdalena, Niklinski Jacek, Kozłowski Miroslaw, Laudanski Jerzy, Szmitkowski Maciej
Department of Biochemical Diagnostics, Medical University, Białystok, Poland.
Acta Biochim Pol. 2013;60(3):489-93. Epub 2013 Sep 19.
Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are present in esophageal cancer cells. Moreover the total activity of ADH as well as the activity of class IV ADH isoenzyme is significantly higher in cancer tissue than in healthy mucosa. The activity of these enzymes in cancer cells is reflected in the sera and could thus be helpful for diagnostics of esophageal cancer. The aim of this study was to investigate a potential significance of ADH isoenzymes and ALDH as tumour markers of esophageal cancer. We defined diagnostic sensitivity, specificity, predictive value for positive and negative results, and receiver-operating characteristics (ROC) curve for tested enzymes.
Serum samples were taken for routine biochemical investigation from 180 patients with esophageal cancer before treatment. Total ADH activity was measured by a photometric method with p-nitrosodimethylaniline as a substrate and ALDH activity by a fluorometric method with 6-methoxy-2-naphtaldehyde as a substrate. For the measurement of the activity of class I and II isoenzymes we employed the fluorometric methods, with class-specific fluorogenic substrates. The activity of class III alcohol dehydrogenase was measured by a photometric method with formaldehyde and class IV with m-nitrobenzaldehyde as a substrate.
There was a significant increase in the activity of class IV of ADH isoenzyme (7.65 mU/l vs 5.88 mU/l) and total ADH activity (1198 mU/l vs 848 mU/l) in the sera of esophageal cancer patients compared to the control. The diagnostic sensitivity for ADH IV was 72%, the specificity 76%, the positive and negative predictive values were 80% and 72% respectively. The area under the ROC curve for ADH IV was 0.65.
The results suggest a potential significance of ADH IV as a marker of esophageal cancer.
酒精脱氢酶(ADH)和乙醛脱氢酶(ALDH)存在于食管癌细胞中。此外,癌组织中ADH的总活性以及IV类ADH同工酶的活性显著高于健康黏膜。这些酶在癌细胞中的活性会反映在血清中,因此可能有助于食管癌的诊断。本研究的目的是探讨ADH同工酶和ALDH作为食管癌肿瘤标志物的潜在意义。我们定义了所检测酶的诊断敏感性、特异性、阳性和阴性预测值以及受试者工作特征(ROC)曲线。
从180例未经治疗的食管癌患者中采集血清样本进行常规生化检查。采用以对亚硝基二甲基苯胺为底物的光度法测定ADH总活性,以6-甲氧基-2-萘甲醛为底物的荧光法测定ALDH活性。对于I类和II类同工酶活性的测定,我们采用了荧光法,使用类特异性荧光底物。采用以甲醛为底物的光度法测定III类酒精脱氢酶的活性,以间硝基苯甲醛为底物测定IV类的活性。
与对照组相比,食管癌患者血清中IV类ADH同工酶的活性(7.65 mU/l对5.88 mU/l)和ADH总活性(1198 mU/l对848 mU/l)显著增加。ADH IV的诊断敏感性为72%,特异性为76%,阳性和阴性预测值分别为80%和72%。ADH IV的ROC曲线下面积为0.65。
结果表明ADH IV作为食管癌标志物具有潜在意义。