8-羟基脱氧鸟苷在结直肠癌患者尿液中的表达

Expression and significance of 8-hydroxy-2′-deoxyguanosine in urine of patients with colorectal cancer

目的研究8-羟基脱氧鸟苷(8-OHdG)在结直肠癌患者尿液中的表达水平及其对结直肠癌的诊断价值。方法收集2015年9月至2016年12月浙江大学医学院附属第二医院58例新近确诊且未接受任何治疗的结直肠癌患者以及26名健康体检者的晨尿样本,运用高效液相色谱(分离)-串联质谱法(HPLC-MS/MS)测定两组尿液中8-OHdG的表达水平。同时,采用化学发光微粒免疫分析法检测受试者的血清癌胚抗原水平。以血清癌胚抗原为对照,利用受试者工作特征(ROC)曲线评价尿液8-OHdG对结直肠癌的诊断价值。结果结直肠癌患者的血清癌胚抗原和尿液8-OHdG水平分别为3.1(2.0,8.3)ng/ml和(1.5±0.8)nmol/mmol肌酐,均高于健康人群[1.8(1.6,2.4)ng/ml,(1.0±0.5)nmol/mmol肌酐,P<0.01],且不同病理分期的患者之间血清癌胚抗原和尿液8-OHdG水平差异有统计学意义(P<0.01)。ROC曲线分析结果显示,以1.95 ng/ml作为诊断临界值,血清癌胚抗原诊断结直肠癌的曲线下面积为0.756,95%CI为0.695~0.818;以1.974 nmol/mmol肌酐为临界值,尿液8-OHdG诊断结直肠癌的曲线下面积为0.843,95%CI为0.774~0.912。结论结直肠癌患者尿液8-OHdG表达水平显著增高,且与癌症病情的进展成正相关,提示尿液8-OHdG可作为一项新的筛查结直肠癌和监测病情进展的生物学指标。

Objective To study the expression level of 8-hydroxy-2'-deoxyguanosine ( 8-OHdG) in urine of patients with colorectal cancer and its value for colorectal cancer diagnosis.Methods Spot morning urine samples from 58 newly diagnosed patients with colorectal cancer( case group) who ware hospitalized in from September 2015 to December 2016 and 26 healthy persons( control group) were collected.The expression level of 8-OHdG in urine was determined by highperformance liquid chromatography ( separation )/mass spectrometry in two groups.Meanwhile, the level of serum carcinoembryonic antigen ( CEA) was detected by chemiluminescent microparticle immunoassay.The diagnostic value of urine 8-OHdG in colorectal cancer was evaluated by receiver operating characteristic ( ROC ) curve with serum carcinoembryonic antigen as control.Results The levels of serum CEA and urinary 8-OHdG in case group were significantly higher than those in control group [3.1( 2.0,8.3) ng /ml vs 1.8( 1.6,2.4) ng /ml,( 1.5 ± 0.8) nmol /mmol creatinine vs ( 1.0 ± 0.5) nmol /mmol creatinine, P < 0.01].There were significant differences in them among patients with different pathological stages( P < 0.01).ROC curve analysis showed that the area under the curve of serum CEA was 0.756( 95% CI = 0.695 - 0.718) with 1.95 ng /ml as the diagnostic threshold and 0.843 ( 95% CI = 0.774 - 0.912) with 1.974 nmol /mmol creatinine as the critical value.Conclusion The expression level of 8-OHdG in urine significantly increases and is positively correlated with the progression of disease in patients with colorectal cancer,suggesting that it can be used as a new biological index for screening colorectal cancer and monitoring the progress of cancer.