论文部分内容阅读
目的分析探讨原发性肝癌(primary hepatic carcinoma,PHC)组织和患者血清中精子相关抗原9(sperm associated antigen 9,SPAG9)的表达水平及对诊断PHC的价值。方法采用免疫组化法检测64例PHC患者癌组织及其匹配癌旁组织中SPAG9和Ki67表达水平,分析SPAG9表达与临床病理资料的关系。用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)和化学发光法定量检测28名健康体检者、7例肝硬化、17例肝炎、56例肝细胞性肝癌、10例肝内胆管癌和5例转移性肝癌患者血清SPAG9抗体和甲胎蛋白(alpha fetoprotein,AFP)浓度;用受试者工作特征(receiver operating characteristic,ROC)曲线评价SPAG9抗体联合AFP诊断PHC的临床价值。结果 PHC患者癌组织中SPAG9阳性率为54.7%(35/64),相应癌旁组织阳性率为23.4%(15/64);二者差异有统计学意义(χ2=18.050,P<0.001)。PHC患者SPAG9阳性率与Ki67阳性率显著正相关(r=0.403,P=0.001);与肿瘤大小、TNM分期、肿瘤数量、淋巴血管侵袭无相关性(χ2值分别为0.479、0.331、2.532、0.740、1.733,P均>0.05)。PHC组血清SPAG9抗体[15.97(8.36~23.84)k IU/L]显著高于肝炎组[4.98(4.03~6.63)k IU/L]和健康对照组[4.96(3.64~8.18)k IU/L,Z值分别为13.83、6.896,P均<0.001];但与肝硬化组[19.10(9.40~20.59)k IU/L]和转移性肝癌组[50.95(6.07~407.95)k IU/L]的差异均无统计学意义(Z值分别为0.096、0.949,P均>0.05)。ROC曲线确定SPAG9和AFP的临界值分别为8.14 k IU/L、14.1μg/L,曲线下面积分别为0.792、0.791,SPAG9抗体和AFP诊断PHC的准确度分别为78.9%(97/123)、77.2%(95/123),敏感度分别为87.9%(58/66)、62.1%(41/66),特异度分别为68.4%(39/57)、94.7%(54/57);两者联合诊断的ROC曲线下面积为0.860,敏感度和特异度分别为90.9%(60/66)、66.7%(38/57),准确度为79.7%(98/123)。以8.14 k IU/L为SPAG9诊断临界值时,6例患者SPAG9抗体表达均阳性(9.37~27.53 k IU/L),其中5例组织中SPAG9免疫组化结果阳性,血清中SPAG9抗体浓度与组织SPAG9表达高度一致。结论 SPAG9及其抗体在PHC癌组织和血清中高表达,血清SPAG9抗体可作为PHC诊断的辅助指标。
Objective To investigate the expression of sperm associated antigen 9 (SPAG9) and its value in the diagnosis of PHC in primary hepatic carcinoma (PHC) tissues and patients. Methods Immunohistochemistry was used to detect the expression of SPAG9 and Ki67 in 64 cases of PHC and their matched paracancerous tissues. The relationship between SPAG9 expression and clinicopathological data was analyzed. 28 healthy subjects, 7 cirrhosis, 17 hepatitis, 56 hepatocellular carcinoma, 10 intrahepatic cholangiocarcinoma and 5 hepatocellular carcinoma were detected by enzyme-linked immunosorbent assay (ELISA) and chemiluminescence The serum SPAG9 antibody and alpha fetoprotein (AFP) concentrations in patients with metastatic liver cancer were measured. The receiver operating characteristic (ROC) curve was used to evaluate the clinical value of SPAG9 antibody in combination with AFP in the diagnosis of PHC. Results The positive rate of SPAG9 in PHC patients was 54.7% (35/64), and the corresponding positive rate in adjacent tissues was 23.4% (15/64). The difference was statistically significant (χ2 = 18.050, P <0.001). The positive rate of SPAG9 in PHC patients was positively correlated with the positive rate of Ki67 (r = 0.403, P = 0.001). There was no correlation between SPAG9 positive rate and tumor size, TNM stage, tumor number and lymphatic vessel invasion (χ2 = 0.479,0.331,2.532,0.740 , 1.733, P> 0.05). The serum SPAG9 antibody [15.97 (8.36-23.84) kIU / L] in PHC group was significantly higher than [4.98 (4.03-6.63) kIU / L] and 4.96 (3.64-8.18) kIU / Z values were 13.83, 6.896, respectively, P <0.001]. However, the difference was statistically significant compared with [19.10 (9.40-20.59) kIU / L] and [50.95 (6.07 ~ 407.95) kIU / L] in liver cirrhosis group There was no statistical significance (Z values were 0.096,0.949, P> 0.05). ROC curve determined the critical value of SPAG9 and AFP were 8.14 kIU / L, 14.1μg / L, the area under the curve were 0.792,0.791, the diagnostic accuracy of SPAG9 antibody and AFP were 78.9% (97/123) The sensitivity was 87.9% (58/66), 62.1% (41/66) and the specificity was 68.4% (39/57) and 94.7% (54/57), respectively The area under the ROC curve for combined diagnosis was 0.860, with a sensitivity and specificity of 90.9% (60/66), 66.7% (38/57) and 79.7% (98/123), respectively. The SPAG9 antibody expression was positive (9.37 ~ 27.53 kIU / L) in all 6 patients at 8.14 kIU / L as the diagnostic value of SPAG9. SPAG9 immunohistochemistry was positive in 5 of the 5 cases, SPAG9 expression is highly consistent. Conclusion SPAG9 and its antibody are highly expressed in the tissues and serums of PHC. The serum SPAG9 antibody can be used as an auxiliary indicator in the diagnosis of PHC.