血清巯基氧化酶-1、甲胎蛋白对原发性肝癌预警和诊断的队列研究-现代医学

血清巯基氧化酶-1、甲胎蛋白对原发性肝癌预警和诊断的队列研究

单位：湖北省武汉市新洲区人民医院检验科, 湖北武汉 431400

分类号：R735.7

出版年·卷·期（页码）：2017·36·第三期（317-323）

摘要：

目的：探讨血清巯基氧化酶-1（QSOX-1）、甲胎蛋白（AFP）对原发性肝癌预警和诊断的价值。方法：从湖北省肝癌高危队列随访及初筛人群样本库中随机选取原发性肝癌患者（肝癌组）60例、肝硬化患者（肝硬化组）60例、慢性乙型肝炎患者（慢乙肝组）60例和正常人群（对照组）60例；另选择同期在武汉市新洲区人民医院住院治疗的60例其他恶性肿瘤患者作为其他肿瘤组，所有受试对象均于清晨空腹时抽取肘静脉血3 ml，采用化学发光法检测血清AFP含量，双抗体夹心法检测血清QSOX-1含量，对肝癌患者进行定期随访，通过绘制ROC曲线分析血清AFP、QSOX-1对原发性肝癌的预测价值。结果：血清AFP、QSOX-1在肝癌组、肝硬化组、慢乙肝组和对照组呈依次递减趋势，肝癌组血清AFP、QSOX-1显著高于肝硬化组、慢乙肝组、其他肿瘤组和对照组（P<0.05），对照组与其他肿瘤组血清QSOX-1比较差异无统计学意义（P>0.05）。有癌栓组血清AFP显著高于无癌栓组，低分化组血清AFP显著高于中分化组、高分化组，Ⅲ～Ⅳ期组血清AFP、QSOX-1显著高于Ⅰ～Ⅱ期组，肿瘤直径≥3 cm组血清AFP、QSOX-1显著高于肿瘤直径<3 cm组，各组间比较差异具有统计学意义（P<0.05）。AFP诊断原发性肝癌的AUC为0.777，当AFP截断值为267.4 mg·L^-1时，其敏感度为47.5%，特异度为76.8%；QSOX-1诊断原发性肝癌的ROC曲线下面积（AUC）为0.878，当QSOX-1截断值为68.75 ng·L^-1时，其敏感度为74.3%，特异度为77.1%；AFP、QSOX-1联合诊断肝癌的敏感度为84.5%，特异度为78.8%。AFP表达阳性组中位生存期为19.8个月，AFP表达阴性组中位生存期为31.7个月，AFP表达阳性组中位生存期显著低于AFP表达阴性组（P<0.05）；QSOX-1表达阳性组中位生存期为12.7个月，QSOX-1表达阴性组中位生存期为28.7个月，QSOX-1表达阳性组中位生存期显著低于QSOX-1表达阴性组（P<0.05）。结论：随着慢性乙型肝炎、肝硬化和肝癌的进展，血清AFP、QSOX-1逐渐升高，血清AFP、QSOX-1联合检测能够为原发性肝癌预警和早期诊断提供依据。

Objective: To explore the early-warning and diagnostic value of alpha fetoprotein(AFP), Quiescin sulfhydl oxidase-1(QSOX-1)for primary liver cancer.Methods: A total of 60 cases of primary hepatocellular carcinoma (HCC group),60 cases of cirrhosis ofthe liver (cirrhosis group),60 cases of chronic hepatitis B patients (chronic hepatitis B group),60 cases of normal person(control group) were randamly selected from follow up of high risk cohort of primary liver cancer in Hubei province and sample bank of screening population,another 60 patients with other malignant tumors, which were treated in the hospital during the same period were selected as the other tumor groups. 3 ml elbow vein blood were extracted from all subjects,the content of serum AFP was detected by Chemiluminescence method, serum QSOX-1 was detected by double antibody sandwich method. The liver cancer patients with regular follow-up,the predictive value of serum AFP and QSOX-1 in primary liver cancer was analyzed by drawn ROC curve.Results: The serum AFP and QSOX-1 was showed a decreased trend in HCC group, cirrhosis group, chronic hepatitis B group and control group,and the serum AFP and QSOX-1 in HCC group were significantly higher than those in cirrhosis group, chronic hepatitis B group, other tumor group and control group (P<0.05),there was no significant difference in serum AFP and QSOX-1 between the control group and other tumor groups (P>0.05).The serum AFP in the tumor thrombus group was significantly higher than that in the non cancerous thrombus group, the serum AFP in the low differentiation group was significantly higher than that in the middle and high differentiation group, the serum levels of AFP and QSOX-1 inⅢ-Ⅳ stage group were significantly higher than those in Ⅰ-Ⅱ stage group,the serum levels of AFP and QSOX-1 in tumor size ≥3 cm group was significantly higher than that of tumor diameter<3 cm group,the differences between the groups with statistically significant (P<0.05).AFP diagnosis of primary liver cancer AUC was 0.777, when the AFP cut-off value was 267.4 mg·L^-1, its sensitivity was 47.5%, the specificity was 76.8%.QSOX-1 diagnosis of primary liver cancer AUC was 0.878, when the QSOX-1 cut-off value was 68.75 ng·L^-1, its sensitivity was 74.3%, the specificity was 77.1%.The sensitivity and specificity of AFP and QSOX-1 combined diagnosis of hepatocellular carcinoma was 84.5% and 78.8%, respectively.The median survival time in AFP expression positive group was 19.8 months, 31.7 months in AFP expression negative group, and the median survival time inAFP expression positive group was significantly lower than that in AFP expression negative group(P<0.05).The median survival time in QSOX-1 expression positive group was 12.7 months, 28.7 months in QSOX-1 expression negative group, and the median survival time inQSOX-1 expression positive group was significantly lower than that in QSOX-1 expression negative group(P<0.05).Conclusion: With the progression of chronic hepatitis B, cirrhosis and liver cancer, the serum AFP and QSOX-1 increase gradually, the combined detection of serum QSOX-1 and AFP can provide the basis for early warning and early diagnosis of primary liver cancer.

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