肝硬化患者血清鳞状细胞癌抗原免疫复合物（SCCA-IgM）水平的逐渐升高与肝细胞癌的发生有关。

Progressive increase of SCCA-IgM immune complexes in cirrhotic patients is associated with development of hepatocellular carcinoma.

作者信息

Pontisso Patrizia, Quarta Santina, Caberlotto Cristina, Beneduce Luca, Marino Maria, Bernardinello Elisabetta, Tono Natascia, Fassina Giorgio, Cavalletto Luisa, Gatta Angelo, Chemello Liliana

机构信息

Clinica Medica 5, Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy.

出版信息

Int J Cancer. 2006 Aug 15;119(4):735-40. doi: 10.1002/ijc.21908.

DOI:10.1002/ijc.21908

PMID:16550605

Abstract

About 3-4% of cirrhotic patients develop primary liver cancer every year. Specific serologic markers have not yet been identified for screening of high risk patients. The serpin squamous cell carcinoma antigen (SCCA) is overexpressed in liver cancer and circulating SCCA-IgM complexes have been described in patients with hepatocellular carcinoma (HCC). The aim of the present study was to assess the behavior of SCCA-IgM in relation to HCC development in patients with cirrhosis. A retrospective, longitudinal study was conducted in a cohort of prospectively followed cirrhotic patients. Two groups with similar clinical profile at presentation were studied : group A included 16 patients who developed HCC during a median follow up of 4 years; group B included 17 patients who did not develop HCC during the same time interval. Circulating SCCA-IgM immune complexes were determined using a recently standardized ELISA assay. At presentation similar levels of SCCA-IgM complexes [mean +/- SD: 267.40 +/- 382.25 U/ml vs. 249.10 +/- 446.90 U/ml, p = 0.9006] and of alpha-fetoprotein [AFP; 24.11 +/- 59.04 IU/ml vs. 10.91 +/- 23.34 IU/ml, p = 0.3995] were detected in group A and in group B. The increase over time (phi) of SCCA-IgM, assessed within at least one year before clinical diagnosis of HCC, was remarkably higher in group A than in group B (mean +/- SD = 280.05 +/- 606.71 (U/ml)/year vs. -37.92 +/- 95.94 (U/ml)/year, p = 0.0408), while AFP increase was not significantly different (11.89 +/- 23.27 (IU/ml)/year vs. 3.67 +/- 11.46 (IU/ml)/year, p = 0.2179). Receiver operating characteristic (ROC) curves were plotted for the rate of change in the levels of both markers and the diagnostic accuracy measured as AUROC was higher for SCCA-IgM phi (0.821) than for AFP phi (0.654). In conclusion, the progressive increase of SCCA-IgM over time was associated with liver tumor development, suggesting that monitoring the behavior of SCCA-IgM might become useful to identify cirrhotic patients at higher risk of HCC development.

摘要

每年约3%-4%的肝硬化患者会发展为原发性肝癌。目前尚未确定用于筛查高危患者的特异性血清学标志物。丝氨酸蛋白酶抑制剂鳞状细胞癌抗原（SCCA）在肝癌中过表达，并且在肝细胞癌（HCC）患者中已发现循环SCCA-IgM复合物。本研究的目的是评估SCCA-IgM与肝硬化患者HCC发生发展的关系。对一组前瞻性随访的肝硬化患者进行了一项回顾性纵向研究。研究了两组就诊时临床特征相似的患者：A组包括16例在中位随访4年期间发生HCC的患者；B组包括17例在同一时间间隔内未发生HCC的患者。使用最近标准化的ELISA测定法测定循环SCCA-IgM免疫复合物。就诊时，A组和B组检测到的SCCA-IgM复合物水平[平均值±标准差：267.40±382.25 U/ml对249.10±446.90 U/ml，p = 0.9006]和甲胎蛋白[AFP；24.11±59.04 IU/ml对10.91±23.34 IU/ml，p = 0.3995]相似。在HCC临床诊断前至少一年内评估的SCCA-IgM随时间的增加（phi），A组明显高于B组（平均值±标准差= 280.05±606.71（U/ml）/年对-37.92±95.94（U/ml）/年，p = 0.0408），而AFP的增加无显著差异（11.89±23.27（IU/ml）/年对3.67±11.46（IU/ml）/年，p = 0.2179）。绘制了两种标志物水平变化率的受试者工作特征（ROC）曲线，以AUROC衡量的诊断准确性，SCCA-IgM phi（0.821）高于AFP phi（0.654）。总之，SCCA-IgM随时间的逐渐增加与肝肿瘤的发生发展相关，这表明监测SCCA-IgM的变化可能有助于识别发生HCC风险较高的肝硬化患者。