Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups
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- 作者：Pavel Sumazin ; Yidong Chen ; Lisa R. Treviño ; Stephen F. Sarabia ; Oliver A. Hampton ; Kayuri Patel ; Toni‐Ann Mistretta ; Barry Zorman ; Patrick Thompson ; Andras Heczey ; et al
- 刊名：Hepatology
- 出版年：2017
- 出版时间：January 2017
- 年：2017
- 卷：65
- 期：1
- 页码：104-121
- 全文大小：1.3MB
- ISSN：1527-3350
文摘
Despite being the most common liver cancer in children, hepatoblastoma (HB) is a rare neoplasm. Consequently, few pretreatment tumors have been molecularly profiled, and there are no validated prognostic or therapeutic biomarkers for HB patients. We report on the first large-scale effort to profile pretreatment HBs at diagnosis. Our analysis of 88 clinically annotated HBs revealed three risk-stratifying molecular subtypes that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways: high-risk tumors were characterized by up-regulated nuclear factor, erythroid 2–like 2 activity; high lin-28 homolog B, high mobility group AT-hook 2, spalt-like transcription factor 4, and alpha-fetoprotein expression; and high coordinated expression of oncofetal proteins and stem-cell markers, while low-risk tumors had low lin-28 homolog B and lethal-7 expression and high hepatic nuclear factor 1 alpha activity. Conclusion: Analysis of immunohistochemical assays using antibodies targeting these genes in a prospective study of 35 HBs suggested that these candidate biomarkers have the potential to improve risk stratification and guide treatment decisions for HB patients at diagnosis; our results pave the way for clinical collaborative studies to validate candidate biomarkers and test their potential to improve outcome for HB patients. (Hepatology 2017;65:104-121).