Serum levels of variants of transthyretin down-regulation in cholangiocarcinoma
Serum levels of variants of transthyretin down-regulation in cholangiocarcinoma
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DOI：
10.1002/jcb.21661
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发表时间：
2008-06-01
影响因子：
4
通讯作者：
He, Dacheng
中科院分区：
文献类型：
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作者：
Liu, Liyun;Wang, Jianing;He, Dacheng
背景：胆管癌（CC）是一种恶性肿瘤，临床诊断特异性生物标志物很少。进行了一项研究，以寻找CC的新血清生物标志物。研究方法：应用表面增强激光解吸电离（SELDI）技术对427例血清标本进行分析，其中包括56例胆囊癌、49例肝胆疾病、269例其他癌症对照和53例健康人。通过SDS-PAGE、ESI/MS-MS、Western blot和免疫沉淀法对候选物进行分离和鉴定。检测CC患者的肝功能，并对部分血清标本进行甲状腺素运载蛋白（TTR）和CA 19 -9的酶联免疫吸附试验（ELISA）。结果：CC组血清中13.76、13.88和14.04km/z峰较对照组明显降低（P < 0.001）。随后，这三个峰被鉴定为天然TTR及其两种变体。ELISA法检测胆囊癌患者血清TTR水平与SELDI法检测结果一致，与健康对照组和良性肝胆疾病组比较差异有显著性（P < 0.001）。CC患者的肝功能检查水平明显升高。TTR联合CA 19 -9鉴别CC与良性肝胆疾病的敏感性为98.2%，特异性为100%。结论：CC患者血清TTR水平明显降低，TTR可作为CA 19 -9诊断CC的补充指标。
Background: Cholangiocarcinoma (CC) is devastating neoplasm and very few specific biomarkers could be used in clinical diagnosis. A study was taken to,find novel serum biomarkers for CC. Methods: Surface enhanced laser desorption/ionization (SELDI) technology was used to analyze427 serum samples including 56 CCs, 49 hepatobiliary diseases, 269 other cancer control, and 53 healthy individuals. The candidates were isolated and identified by SDS-PAGE, ESI/MS-MS, Western blot, and immunoprecipitation. Liver functions of CC patients were examined and enzyme-linked irnmunosorbent assay (ELISA) of transthyretin (TTR) and CA19-9 were further performed in some sets of serum samples. Results: 13.76,13.88, and 14.04 k m/z peaks in sera were significantly decreased in CC compared with the control groups (P < 0.001). Subsequently, these three peaks were identified as native TTR and its two variants. ELISA assay indicated that TTR levels were consistent with SELDI analysis in CC compared with healthy control and benign diseases of hepatobiliary (P < 0.001). Liver function test levels were obviously elevated for CC patients. TTR combining with CA19-9 to differentiate CC from benign hepatobiliary diseases showed sensitivity and specificity were 98.2% and 100%, respectively. Conclusion: The levels of TTR were significantly down-regulated in sera of CC patients and may be complementary markers of CA19-9 in diagnosis for CC.