Beckebaum S, Chen X, Sotiropoulos G C, Radtke A, Daoudaki M, Baba H A, Wohlschlaeger J, Broelsch C E, Gerken G, Cicinnati V R
Department of Gastroenterology and Hepatology, Department of General, Visceral, and Transplantation Surgery, University Hospital Essen, University of Duisburg, Essen, Germany.
Transplant Proc. 2008 Nov;40(9):3182-4. doi: 10.1016/j.transproceed.2008.08.034.
Detection of new biomarkers for hepatocellular carcinoma (HCC) is needed to estimate prognosis after liver transplantation (OLT) or hepatic resection. Osteopontin (OPN) is a secreted, calcium-binding, phosphorylated, acidic glycoprotein that is overexpressed in various cancers. Cluster differentiation 44 standard isoform (CD44s) is one of the primary receptors of OPN; it may contribute to metastatic tumor spread.
Tumor tissue and surrounding hepatic parenchyma were obtained from 53 HCC patients who underwent liver resection. Their RNA was extracted from nitrogen-frozen tissues, and OPN mRNA levels were estimated by quantitative reverse transcription-polymerase chain reactions. Formalin-fixed, paraffin-embedded tissues were obtained from the same patients, and additionally from 60 OLT HCC patients to perform expression analysis for OPN and CD44s by standard avidin-biotin immunostaining methods.
Expression of OPN and CD44s was significantly higher among HCC compared with adjacent nontumor tissue. The OPN mRNA expression and protein abundance correlated positively; OPN overexpression was associated with high tumor grade. A positive correlation existed between OPN and CD44s expression; both proteins were significantly overexpressed in HCC lesions with positive lymph nodes. No significant correlation existed between patient survival and OPN and CD44s expression.
Expression of both OPN and CD44s in HCC is associated with advanced tumor stage, thus possibly contributing prognostic information when evaluated together with classical clinicopathological parameters.
需要检测肝细胞癌（HCC）的新生物标志物，以评估肝移植（OLT）或肝切除术后的预后。骨桥蛋白（OPN）是一种分泌型、钙结合、磷酸化的酸性糖蛋白，在多种癌症中过度表达。簇分化44标准异构体（CD44s）是OPN的主要受体之一；它可能有助于转移性肿瘤的扩散。
从53例行肝切除的HCC患者中获取肿瘤组织和周围肝实质。从液氮冷冻组织中提取RNA，通过定量逆转录聚合酶链反应估计OPN mRNA水平。从同一患者以及另外60例OLT HCC患者中获取福尔马林固定、石蜡包埋的组织，采用标准抗生物素蛋白-生物素免疫染色方法对OPN和CD44s进行表达分析。
与相邻非肿瘤组织相比，HCC中OPN和CD44s的表达显著更高。OPN mRNA表达与蛋白丰度呈正相关；OPN过表达与高肿瘤分级相关。OPN与CD44s表达之间存在正相关；在有阳性淋巴结的HCC病变中，这两种蛋白均显著过表达。患者生存率与OPN和CD44s表达之间无显著相关性。
HCC中OPN和CD44s的表达均与肿瘤晚期相关，因此与经典临床病理参数一起评估时可能有助于提供预后信息。
