Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinoma
Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinoma
复制标题
作者：
Pan, HW;Ou, YH;Hsu, HC
背景。经门静脉扩散的肝内转移是肝细胞癌（HCC）的重要特征和重要的不良预后因素。为了确定肿瘤进展的分子因素，作者使用差异显示 (DD) 来分析 HCC 中的异常基因表达。本研究的目的是阐明骨桥蛋白 (OPN) 在 HCC 进展中的临床病理学和预后意义。 OPN mRNA 水平在 DD 测定中在 HCC 中优先增加，并通过 Northern 印迹进行验证，在指数期使用逆转录聚合酶链反应在 240 个手术切除的单灶原发性 HCC 中进行测量。 OPN mRNA 表达与临床病理特征相关，特别是门静脉侵犯、早期肿瘤复发和预后。结果。骨桥蛋白 mRNA 在 133 个肿瘤 (55%) 中过度表达。 OPN过表达与甲胎蛋白升高（P = 0.001）、p53突变（P = 0.021）、较大肿瘤（P = 0.002）、高级别HCC（P < 0.001）、晚期HCC（P < 0.001）、早期肿瘤复发和/或转移（P = 0.003）以及较低的10年生存率密切相关（P = 0.00013）。多变量分析显示肿瘤分期和早期肿瘤复发是关键的预后因素。在早期 HCC 中，与晚期 HCC 相比，没有血管侵犯，早期肿瘤复发率较低，OPN mRNA 过表达预示着较高的早期复发率 (P = 0.003)。 结论。 OPN mRNA过表达与肿瘤高级别、晚期和早期复发密切相关，导致预后较差。骨桥蛋白过度表达可能是一个不利的预后因素，也是预测早期 HCC 早期复发的有用标志物。癌症 2003；98：119-27。 (C) 2003 年美国癌症协会。
BACKGROUND. Intrahepatic metastasis via portal vein spread is an important feature and a crucial unfavorable prognostic factor of hepatocellular carcinoma (HCC). To identify the molecular factors for tumor progression, the authors used differential display (DD) to analyze aberrant gene expression in HCC. The goal of the current study was to elucidate the clinicopathologic and prognostic significance of osteopontin (OPN) in HCC progression.METHODS. OPN mRNA levels, which were increased preferentially in HCC in a DD assay and verified with Northern blotting, were measured in 240 surgically removed, unifocal, primary HCCs using the reverse transcription-polymerase chain reaction at the exponential phase. OPN mRNA expression was correlated with clinicopathologic features, particularly portal vein invasion, early tumor recurrence, and prognosis.RESULTS. Osteopontin mRNA was overexpressed in 133 tumors (55%). The OPN overexpression was associated closely with a-fetoprotein elevation (P = 0.001), p53 mutation (P = 0.021), larger tumors (P = 0.002), high-grade HCC (P < 0.001), late-stage HCC (P < 0.001), early tumor recurrence and/or metastasis (P = 0.003), and a lower 10-year survival rate (P = 0.00013). Multivariate analysis revealed that tumor stage and early tumor recurrence were crucial prognostic factors. In early-stage HCC, which has no vascular invasion and a lower early tumor recurrence than late-stage HCC, OPN mRNA overexpression predicted a higher early recurrence rate (P = 0.003).CONCLUSIONS. OPN mRNA overexpression was correlated closely with high-grade, late-stage, and early tumor recurrence, which lead to poorer prognosis. Osteopontin overexpression might serve as an unfavorable prognostic factor and a useful marker for predicting early recurrence in early-stage HCC. Cancer 2003;98:119-27. (C) 2003 American Cancer Society.