Pavel Sumazin1,2,3, Yidong Chen4, Lisa R Treviño5,6, Stephen F Sarabia7, Oliver A Hampton5,6, Kayuri Patel7, Toni-Ann Mistretta7, Barry Zorman1,2, Patrick Thompson1,2, Andras Heczey1,2,3, Sarah Comerford8, David A Wheeler5,6, Murali Chintagumpala1,2,3, Rebecka Meyers9, Dinesh Rakheja10, Milton J Finegold1,2,3,7, Gail Tomlinson11, D Williams Parsons1,2,3,5,6, Dolores López-Terrada1,2,3,7. 1. Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX. 2. Department of Pediatrics, Baylor College of Medicine, Houston, TX. 3. Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX. 4. Departments of Epidemiology and Biostatistics, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX. 5. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX. 6. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX. 7. Pathology & Immunology, Baylor College of Medicine, Houston, TX. 8. Departments of Molecular Genetics and Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX. 9. Department of Pediatric Surgery, University of Utah, Salt Lake City, UT. 10. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX. 11. Departments of Pediatric Hematology and Oncology, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX.
Abstract
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).
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).
Authors: Hua-Sheng Chiu; María Rodríguez Martínez; Elena V Komissarova; David Llobet-Navas; Mukesh Bansal; Evan O Paull; José Silva; Xuerui Yang; Pavel Sumazin; Andrea Califano Journal: Nucleic Acids Res Date: 2018-05-18 Impact factor: 16.971
Authors: Jie Zhang; Pin Liu; Junyan Tao; Pan Wang; Yi Zhang; Xinhua Song; Li Che; Pavel Sumazin; Silvia Ribback; Andras Kiss; Zsuzsa Schaff; Antonio Cigliano; Frank Dombrowski; Carla Cossu; Rosa M Pascale; Diego F Calvisi; Satdarshan P Monga; Xin Chen Journal: Am J Pathol Date: 2019-02-19 Impact factor: 4.307
Authors: Weiqi Zhang; Jennifer Meyfeldt; Huabo Wang; Sucheta Kulkarni; Jie Lu; Jordan A Mandel; Brady Marburger; Ying Liu; Joanna E Gorka; Sarangarajan Ranganathan; Edward V Prochownik Journal: J Biol Chem Date: 2019-10-09 Impact factor: 5.157