酶法检测唾液酸的性能验证及临床应用评估

Evaluation of serum sialic acid detection kit using enzymic method and investigate the clinical diagnosis value of sialic acid

目的 对酶法检测唾液酸（SA）的检测性能进行评价,并对SA的临床应用进行评估.方法 回顾性病例对照研究.检测150名表面健康人血清SA水平,建立参考区间;评估酶法检测SA的准确度、精密度、线性;对240例肿瘤患者按病理类型分组后,比较各肿瘤组血清SA浓度与健康对照组是否存在差异;对于存在差异的肿瘤,进一步收取疾病对照组,通过绘制ROC曲线,评价SA与其他肿瘤标志物的诊断性能.采用t检验、ANOVA方差分析、Mann-Whitney U检验进行统计学分析.结果 150名表面健康人血清SA水平为479～715 mg/L;2个水平质控检测结果为584、1 482 mg/L,均在厂商允许偏差范围之内,批内、批间变异系数（CV）＜5％,0～1 052 mg/L范围内线性良好（Y=0.995X-0.177,R2 =0.999）.胃癌组、对应良性疾病对照组、健康对照组的SA水平分别为（757±177）、（514±86）、（597±60）mg/L,差异有统计学意义（F =55.2,P＜0.01）.结直肠癌组、对应良性疾病对照组的SA水平分别为（659±127）、（545±66） mg/L,差异有统计学意义（F=42.8,P＜0.01）.肺癌组、对应良性疾病对照组的SA水平分别为（738±157）、（672±161） mg/L,其差异无统计学意义（F=26.3,P＞0.05）.SA在胃癌组中的曲线下面积（AUC）为0.804,结直肠癌组为0.724,肺癌组为0.755.在胃癌组中,SA的诊断敏感度为59.5％,优于CEA的24.3％;在CEA未增高的肿瘤患者中,SA在胃癌组中的AUC为0.791,结直肠癌组为0.687.结论 酶法SA检测性能符合要求.在胃癌组中SA的诊断性能优于传统标志物CA72-4和CEA,可以辅助CEA对部分肿瘤患者进行筛选和诊断.

Objective To evaluate the performance of serum sialic acid detection kit using enzymic method and investigate the clinical diagnosis value of sialic acid.Methods one hundred and fifty healthy adults were enrolled in this case control study to establish serum SA reference interval.The analytical performance （accuracy,precision,linearity） of serum sialic acid detection kit using enzymic method was assessed.Two hundred and forty patients were classified into different malignant tumor groups according to their pathological types.Serum SA level of each tumor group was compared with that of normal control group.In tumor groups with statistical difference,benign disease groups were further collected.Receiver operating characteristic （ROC） curve and area under curve （AUC） were used to evaluate the diagnostic value of SA compared with other tumor markers.t test,one-way ANOVA,Mann-Whitney U test were used as statistical methods.Results The reference interval of SA was 479 to 715 mg/L.The detection result of 2 level controls was 584 and 1 482 mg/L respectively,which were both within the acceptable limits.The within-lot and between-lot variations of three level samples were both below 5%.There was a good linear correlation （Y =0.995X-0.177,R2 =0.999） between theoretical value and actual detection result in range of 0-1 052 mg/L.The serum level of SA was （757 ± 177）,（514 ± 86） and （597 ± 60） mg/L in gastric cancer group,benign disease control group and normal control group respectively,which had statistically significant difference（F =55.2,P 〈 0.01）.The serum level of SA was（659 ± 127） and （545 ± 66） mg/L in colorectal cancer group and benign disease control group respectively,which had statistically significant difference（F =42.8,P 〈 0.01）.The serum level of SA was （738 ± 157） and （672 ± 161） mg/L in colorectal cancer group and benign disease control group respectively,which did not have statistically significant difference（F =26.3,P 〉 0.05）.The AUC of SA was 0.804,0.724,0.755 in gastric cancer group,colorectal cancer group and lung cancer group respectively,which was higher than that of CEA and CA72-4.In gastric cancer group,the sensitivity of SA was higher than that of CEA （59.5%,24.3%）.The AUC of SA was 0.791,0.687,0.790 in gastric cancer,colorectal cancer and lung cancer patients with normal CEA serum level respectively.Conclusions Experimental results show that serum sialic acid detection kit using enzymic method has good performance in the precision and linearity.Sialic acid has some value in the diagnosis of gastric cancer and colorectal cancer and could be a good supplement of CEA in screening of cancer.