|Title:||ASPM\s a novel marker for vascular invasion, early recurrence, and poor prognosis of hepatocellular carcinoma||Authors:||Lin S.-Y.
|Issue Date:||2008||Journal Volume:||14||Journal Issue:||15||Start page/Pages:||4814||Source:||Clinical Cancer Research||Abstract:||
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. ASPMoverexpression correlated with high α-fetoprotein (P = 1 × 10-8), high-grade (grade ll-IV) HCC (P - 2 × 10-6), high-stage (stage IIIA-IV) HCC (P = 1 × 10-8), and importantly ETR (P = 1 × 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 α-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 × 10-8), whereas ASPM overexpression (odds ratio, 6.49; P = 1 × 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 × 10-8) and non-p53-mutated HCC (P = 1 × 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. ? 2008 American Association for Cancer Research.
|ISSN:||1078-0432||DOI:||10.1158/1078-0432.CCR-07-5262||SDG/Keyword:||alpha fetoprotein; messenger RNA; protein p53; ASPM protein, human; nerve protein; protein p53; abnormal spindle like microcephaly associated gene; adolescent; adult; aged; article; benign tumor; cancer grading; cancer staging; cancer survival; female; fetus (anatomy); gene; human; human tissue; liver cell carcinoma; liver tumor; major clinical study; male; nucleotide sequence; priority journal; prognosis; reverse transcription polymerase chain reaction; risk factor; tumor growth; tumor recurrence; tumor volume; biosynthesis; blood vessel; cancer invasion; disease course; gene expression regulation; genetics; liver cell carcinoma; liver tumor; metabolism; metastasis; middle aged; pathology; Aged; Blood Vessels; Carcinoma, Hepatocellular; Disease Progression; Female; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Nerve Tissue Proteins; Prognosis; Tumor Suppressor Protein p53
|Appears in Collections:||病理學科所|
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