ASPM is a novel marker for vascular invasion, early recurrence, and poor prognosis of hepatocellular carcinoma
ASPM is a novel marker for vascular invasion, early recurrence, and poor prognosis of hepatocellular carcinoma
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DOI：
10.1158/1078-0432.ccr-07-5262
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发表时间：
2008-08-01
影响因子：
11.5
通讯作者：
Hsu, Hey-Chi
中科院分区：
文献类型：
--
作者：
Lin, Shih-Yeh;Pan, Hung-Wei;Hsu, Hey-Chi
目的：异常梭形小头畸形（ASPM）在神经发生和细胞增殖中起重要作用。本研究采用逆转录-聚合酶链反应（RT-PCR）技术检测了247例肝细胞癌（HCC）组织中ASPM mRNA的表达，并与临床病理和分子生物学特征进行了相关性分析。ASPM mRNA在162例HCC中过表达（66%），而在良性肝肿瘤中无表达。ASPM过表达与高甲胎蛋白（P = 1 × 10 - 8）、高级别（II-IV级）HCC（P = 2 × 10 - 6）、高分期（IIIA-IV期）HCC（P = 1 × 10-8）以及重要的ETR（P = 1 × 10 - 8）相关。ETR是最重要的临床预后不良因素。在各种独立的组织病理学（肿瘤大小、肿瘤分级和肿瘤分期）和分子因素（p53突变，高ET-甲胎蛋白，ASPM过度表达），肿瘤分期是最关键的组织学因素（比值比，14.7; 95%置信区间，6.65-33.0; P = 1 × 10（-8）），而ASPM过表达（比值比，6.49; P = 1 × 10（-8））是与ETR相关的最重要的分子因素。ASPM过表达与p53突变（所有P值均为1 × 10（-8））和非p53突变HCC（P值分别为1 × 10（-8）和0.00088）的血管浸润和ETR相关。因此，APSM过表达HCC患者在p53突变（P = 0.00008）和非p53突变HCC（P = 0.0027）中的5年生存率较低（P = 0.000001）。在低分期（II期）HCC中，ASPM过表达与ETR增高相关（P0.008）。结论：ASPM过表达是HCC侵袭转移潜能增强、ETR增高的分子标志物，与p53突变状态和肿瘤分期无关，因此预后不良。
Purpose: Abnormal spindle-like microcephaly associated (ASPM) plays an important role in neurogenesis and cell proliferation. This study is to elucidate its role in hepatocellular carcinoma (HCC), particularly early tumor recurrence (ETR) and prognosis.Experimental Design: We used reverse transcription-PCR assays to measure the Aspm mRNA levels in 247 HCC and correlated with clinicopathologic and molecular features.Results: ASPM mRNA levels were high in fetal tissues but very low in most adult tissues. ASPM mRNA was overexpressed in 162 HCC (66%) but not in benign liver tumors. ASPM overexpression correlated with high alpha-fetoprotein (P = 1 x 10(-8)), high-grade (grade II-IV) HCC (P = 2 x 10(-6)), high-stage (stage IIIA-IV) HCC (P = 1 x 10-8), and importantly ETR (P = 1 x 10(-8)). ETR is the most critical unfavorable clinical prognostic factor. Among the various independent histopathologic (tumor size, tumor grade and tumor stage) and molecular factors (p53 mutation, high et-fetoprotein, and ASPM overexpression), tumor stage was the most crucial histologic factor (odds ratio, 14.7; 95% confidence interval, 6.65-33.0; P = 1 x 10(-8)), whereas ASPM overexpression (odds ratio, 6.49; P = 1 x 10(-8)) is the most important molecular factor associated with ETR. ASPM overexpression was associated with vascular invasion and ETR in both p53-mutated (all P values = 1 x 10(-8)) and non-p53-mutated HCC (P = 1 x 10(-8) and 0.00088, respectively). Hence, patients with APSM-overexpressing HCC had lower 5-year survival (P = 0.000001) in both p53-mutated (P = 0.00008) and non-p53-mutated HCC (P = 0.0027). In low-stage (stage II) HCC, ASPM overexpression also correlated with higher ETR (P 0.008).Conclusion: ASPM overexpression is a molecular marker predicting enhanced invasive/metastatic potential of HCC, higher risk of ETR regardless of p53 mutation status and tumor stage, and hence poor prognosis.