血浆Rap2a蛋白在肝癌中的表达及诊断价值

Expression of plasma Rap2a protein in hepatocellular carcinoma and its diagnostic value

目的探讨血浆Rap2a蛋白表达对肝癌的诊断价值。方法 41例肝癌患者为肝癌组,28例肝硬化患者为肝硬化组,30例体检健康者为对照组,采用ELISA法检测3组血浆Rap2a蛋白及甲胎蛋白(alpha-fetoprotein, AFP)水平,分析Rap2a蛋白表达与肝癌临床特征的关系;采用Spearman法分析Rap2a与AFP的相关性;绘制ROC曲线,评估Rap2a对肝癌的诊断效能。结果肝癌组血浆Rap2a蛋白[118.57(73.99,153.44)μg/L]和AFP[148.51(37.42,295.77)μg/L]水平高于肝硬化组[64.73(34.54,75.86)、38.61(18.76,72.42)μg/L]和对照组[17.63(8.94,24.53)、21.98(12.24,49.27)μg/L](P<0.05),肝硬化组与对照组比较差异无统计学意义(P>0.05);肝癌组血浆Rap2a蛋白水平与AFP水平无相关性(r=-0.258,P=0.103);肝癌组TNM分期Ⅲ～Ⅳ期和有远处转移者血浆Rap2a蛋白水平[139.94(80.31,230.52)μg/L,167.16(107.29,399.56)μg/L]明显高于Ⅰ～Ⅱ期[104.57(36.41,131.27)μg/L]和无远处转移者[103.07(42.46,131.27)μg/L](P<0.05),血浆Rap2a蛋白水平在不同年龄、性别、肿瘤直径、乙型肝炎病毒感染状态及有无门静脉血管侵犯方面差异无统计学意义(P>0.05);以Rap2a蛋白水平78.57μg/L为最佳截断值时,诊断肝癌的AUC为0.868(95%CI:0.784～0.952),灵敏度为83.6%,特异度为78.3%;Rap2a与AFP联合检测诊断肝癌的AUC(0.985)高于Rap2a或AFP单独检测的AUC(0.868,0.783)(P<0.05)。结论 Rap2a诊断肝癌有较高敏感度与特异度,有可能成为诊断肝癌的一种新肿瘤标志物;Rap2a与AFP联合检测可提高肝癌的诊断率。

Objective To investigate the value of plasma Rap2 a protein to the diagnosis of hepatocellular carcinoma(HCC). Methods The levels of plasma Rap2 a protein and alpha-fetoprotein(AFP) were detected by ELISA in 41 patients with HCC(HCC group), 28 patients with liver cirrhosis(cirrhosis group) and 30 healthy volunteers(control group). The relationship between Rap2 a protein expression and clinical features of HCC was analyzed. Spearman method was used to analyze the correlation between Rap2 a and AFP. The diagnostic efficiency of Rap2 a for HCC was evaluated by ROC. Results The levels of plasma Rap2 a protein and AFP were significantly higher in HCC group(118.57(73.99, 153.44), 148.51(37.42, 295.77)μg/L) than those in cirrhosis group(64.73(34.54, 75.86), 38.61(18.76, 72.42)μg/L) and control group(17.63(8.94, 24.53), 21.98(12.24, 49.27)μg/L)(P<0.05), and showed no significant differences between cirrhosis group and control group(P>0.05). There was no correlation between Rap2 a level and AFP level(r=-0.258, P=0.103). The level of plasma Rap2 a protein was significantly higher in patients with TNM stage Ⅲ-Ⅳ(139.94(80.32, 230.52)μg/L) and with distant metastasis(167.16(107.29, 399.56)μg/L) than that in patients with TNM stage Ⅰ-Ⅱ(104.57(36.41, 131.27)μg/L) and no distant metastasis(103.07(42.46, 131.27)μg/L) in HCC group(P<0.05), and showed no significant difference between patients in different age, sex, tumor diameter, hepatitis B virus infection status and presence or absence of portal vascular invasion(P>0.05). When the optimal cut-off value of Rap2 a was 78.57 μg/L, the AUC for the diagnosis of HCC was 0.868(95%CI: 0.784-0.952), the sensitivity was 83.6%, and the specificity was 78.3%. The AUC of Rap2 a combined with AFP was 0.985, significantly higher than that of Rap2 a or AFP alone(0.868, 0.783)(P<0.05). Conclusion Rap2 a has a high sensitivity and specificity for the diagnosis of HCC, and might be used as a new tumor marker. The joint detection of Rap2 a and AFP levels can improve the diagnosis rate of HCC.