Digestive Disease and Life-style Related Disease Health Research, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
J Gastroenterol. 2010 Apr;45(4):459-67. doi: 10.1007/s00535-009-0160-5. Epub 2009 Dec 9.
Hepatocellular carcinoma (HCC) has a high mortality rate, and early detection of HCC improves patient survival. However, the molecular diagnostic markers for early HCC have not been fully elucidated. The aim of this study was to identify novel diagnostic markers for HCC.
Serum protein profiles of 45 hepatitis C virus infection (HCV)-related HCC patients (HCV-HCC) were compared to 42 HCV-related chronic liver disease patients without HCC (HCV-CLD) and 21 healthy volunteers using the ProteinChip SELDI system. One of the identified proteins was evaluated as a diagnostic marker for HCC in patients with HCV.
Five protein peaks (4067, 4470, 7564, 7929, and 8130 m/z) had p-values less than 1 x 10(-7) and were significantly increased in the sera of HCV-HCC patients compared to HCV-CLD patients and healthy volunteers. Among these proteins, an 8130 m/z peak was the most differentially expressed and identified as the complement component 3a (C3a) fragment. For HCV-HCC and HCV-CLD, the relative intensity of this C3a fragment had the best area under the ROC curve [0.70], followed by des-gamma-carboxy prothrombin (DCP) [0.68], lectin-bound alpha fetoprotein (AFP-L3) [0.58] and AFP [0.53] for HCC. A combined analysis of the C3a fragment, AFP and DCP led to a 98% positive identification rate. In addition, the measurable C3a fragment in some HCC patients was not only significantly higher in the year of HCC onset compared to the pre-onset year, but also decreased after treatment.
The 8130 m/z C3a fragment is a potential marker for the early detection of HCV-related HCC.
肝细胞癌(HCC)死亡率高,早期发现 HCC 可提高患者生存率。然而,HCC 的分子诊断标志物尚未完全阐明。本研究旨在寻找 HCC 的新型诊断标志物。
应用 ProteinChip SELDI 系统比较 45 例丙型肝炎病毒(HCV)相关 HCC 患者(HCV-HCC)、42 例无 HCC 的 HCV 相关慢性肝病患者(HCV-CLD)和 21 例健康志愿者的血清蛋白图谱。对鉴定出的一种蛋白作为 HCV 患者 HCC 的诊断标志物进行评价。
与 HCV-CLD 患者和健康志愿者相比,HCV-HCC 患者血清中 5 种蛋白峰(4067、4470、7564、7929 和 8130 m/z)的 p 值<1×10(-7),且显著升高。其中,8130 m/z 峰差异表达最显著,鉴定为补体成分 3a(C3a)片段。对于 HCV-HCC 和 HCV-CLD,该 C3a 片段的相对强度具有最佳的 ROC 曲线下面积[0.70],其次是脱-γ-羧基凝血酶原(DCP)[0.68]、结合型α-L-岩藻糖苷酶(AFP-L3)[0.58]和 AFP[0.53]。C3a 片段、AFP 和 DCP 的联合分析可使 HCC 的阳性识别率达到 98%。此外,部分 HCC 患者的可测量 C3a 片段在 HCC 发病当年明显高于发病前一年,且治疗后降低。
8130 m/z C3a 片段是一种早期检测 HCV 相关 HCC 的潜在标志物。