Dept of Medicine, University of Padua, Padua, Italy.
Unit of Hepatobiliary Surgery and Liver Transplantation, University of Padua, Padua, Italy.
Br J Cancer. 2014 May 27;110(11):2708-15. doi: 10.1038/bjc.2014.246. Epub 2014 May 8.
Hepatocellular carcinoma (HCC) is one of the most important sanitary problems for its prevalence and poor prognosis. To date, no information is available on the prognostic value of the ov-serpin SERPINB3, detected in primary liver cancer but not in normal liver. The aim of the study was to analyse SERPINB3 expression in liver cancer in relation with molecular signatures of poor prognosis and with clinical outcome.
Liver tumours of 97 patients were analysed in parallel for SERPINB3, TGF-β and β-catenin. In a subgroup of 67 patients with adequate clinical follow-up, the correlation of molecular findings with clinical outcome was also carried out.
High SERPINB3 levels were detectable in 22% of the patients. A significant correlation of this serpin with TGF-β at transcription and protein level was observed, whereas for β-catenin a strong correlation was found only at post-transcription level. These findings were in agreement with transcriptome data meta-analysis, showing accumulation of SERPINB3 in the poor-prognosis subclass (S1). High levels of this serpin were significantly associated with early tumour recurrence and high SERPINB3 was the only variable significantly associated with time to recurrence at multivariate analysis.
SERPINB3 is overexpressed in the subset of the most aggressive HCCs.
肝细胞癌 (HCC) 是一个重要的卫生问题，因为其发病率高且预后不良。迄今为止，尚无关于在原发性肝癌中检测到但在正常肝脏中未检测到的 ov-serpin SERPINB3 的预后价值的信息。本研究旨在分析 SERPINB3 在肝癌中的表达与不良预后的分子特征以及临床结果的关系。
对 97 例患者的肝脏肿瘤进行平行分析，以检测 SERPINB3、TGF-β 和 β-catenin。在 67 例具有充足临床随访的患者亚组中，还进行了分子发现与临床结果的相关性分析。
在 22%的患者中可检测到高水平的 SERPINB3。观察到该丝氨酸蛋白酶与转录和蛋白水平的 TGF-β 显著相关，而对于 β-catenin，仅在转录后水平发现强烈相关性。这些发现与转录组数据荟萃分析一致，表明 SERPINB3 在预后不良亚组 (S1) 中积累。高水平的这种丝氨酸蛋白酶与肿瘤早期复发显著相关，并且在多变量分析中，高 SERPINB3 是唯一与复发时间显著相关的变量。
SERPINB3 在最具侵袭性的 HCC 亚组中过度表达。
