title: Integrated Proteomic and Transcriptomic-Based Approaches to Identifying Signature Biomarkers and Pathways for Elucidation of Daoy and UW228 Subtypes.
abstract: Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Patient survival has remained largely the same for the past 20 years, with therapies causing significant health, cognitive, behavioral and developmental complications for those who survive the tumor. In this study, we profiled the total transcriptome and proteome of two established MB cell lines, Daoy and UW228, using high-throughput RNA sequencing (RNA-Seq) and label-free nano-LC-MS/MS-based quantitative proteomics, coupled with advanced pathway analysis. While Daoy has been suggested to belong to the sonic hedgehog (SHH) subtype, the exact UW228 subtype is not yet clearly established. Thus, a goal of this study was to identify protein markers and pathways that would help elucidate their subtype classification. A number of differentially expressed genes and proteins, including a number of adhesion, cytoskeletal and signaling molecules, were observed between the two cell lines. While several cancer-associated genes/proteins exhibited similar expression across the two cell lines, upregulation of a number of signature proteins and enrichment of key components of SHH and WNT signaling pathways were uniquely observed in Daoy and UW228, respectively. The novel information on differentially expressed genes/proteins and enriched pathways provide insights into the biology of MB, which could help elucidate their subtype classification.
authors.affiliation: Bioinformatics and High-Throughput Analysis Laboratory, Seattle Children's Research Institute, Seattle, WA 98101, USA. roghig@yahoo.com.|Data and Analytics, Seattle Children's Hospital, Seattle, WA 98101, USA. roghig@yahoo.com.|Data-Enabled Life Sciences Alliance (DELSA), Seattle, WA 98101, USA. roghig@yahoo.com.|High-Throughput Analysis Core, Seattle Children's Research Institute, Seattle, WA 98101, USA. roghig@yahoo.com.
authors.forename: Roger
authors.initials: R
authors.lastname: Higdon
authors.affiliation: Department of Chemistry and Biological Sciences, Macquarie University, Sydney 2109, Australia. jessiekala7@yahoo.com.
authors.forename: Jessie
authors.initials: J
authors.lastname: Kala
authors.affiliation: Department of Chemistry and Biological Sciences, Macquarie University, Sydney 2109, Australia. wilkins.devan@gmail.com.
authors.forename: Devan
authors.initials: D
authors.lastname: Wilkins
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA. fangfei3.yan@gmail.com.
authors.forename: Julia Fangfei
authors.initials: JF
authors.lastname: Yan
authors.affiliation: Department of Chemistry and Biological Sciences, Macquarie University, Sydney 2109, Australia. manveen.sethi@students.mq.edu.au.
authors.forename: Manveen K
authors.initials: MK
authors.lastname: Sethi
authors.affiliation: Beijing Genomics Institute, Shenzhen 518083, Guangdong, China. linl@genomics.org.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Lin
authors.affiliation: Beijing Genomics Institute, Shenzhen 518083, Guangdong, China. siqiliu@genomics.org.cn.|Chinese Academy of Sciences, Beijing 100101, China. siqiliu@genomics.org.cn.
authors.forename: Siqi
authors.initials: S
authors.lastname: Liu
authors.affiliation: Bioinformatics and High-Throughput Analysis Laboratory, Seattle Children's Research Institute, Seattle, WA 98101, USA. elizabeth.montague@seattlechildrens.org.|Data and Analytics, Seattle Children's Hospital, Seattle, WA 98101, USA. elizabeth.montague@seattlechildrens.org.|Data-Enabled Life Sciences Alliance (DELSA), Seattle, WA 98101, USA. elizabeth.montague@seattlechildrens.org.|High-Throughput Analysis Core, Seattle Children's Research Institute, Seattle, WA 98101, USA. elizabeth.montague@seattlechildrens.org.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Montague
authors.affiliation: Data and Analytics, Seattle Children's Hospital, Seattle, WA 98101, USA. imrepnw@live.com.|Data-Enabled Life Sciences Alliance (DELSA), Seattle, WA 98101, USA. imrepnw@live.com.|High-Throughput Analysis Core, Seattle Children's Research Institute, Seattle, WA 98101, USA. imrepnw@live.com.
authors.forename: Imre
authors.initials: I
authors.lastname: Janko
authors.affiliation: Bioinformatics and High-Throughput Analysis Laboratory, Seattle Children's Research Institute, Seattle, WA 98101, USA. john.choiniere@gmail.com.|Data and Analytics, Seattle Children's Hospital, Seattle, WA 98101, USA. john.choiniere@gmail.com.|Data-Enabled Life Sciences Alliance (DELSA), Seattle, WA 98101, USA. john.choiniere@gmail.com.
authors.forename: John
authors.initials: J
authors.lastname: Choiniere
authors.affiliation: Data and Analytics, Seattle Children's Hospital, Seattle, WA 98101, USA. ncherryus@gmail.com.|Data-Enabled Life Sciences Alliance (DELSA), Seattle, WA 98101, USA. ncherryus@gmail.com.|High-Throughput Analysis Core, Seattle Children's Research Institute, Seattle, WA 98101, USA. ncherryus@gmail.com.
authors.forename: Natali
authors.initials: N
authors.lastname: Kolker
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA. wi.hancock@neu.edu.|Department of Biomedical Sciences, Macquarie University, Sydney NSW 2109, Australia. wi.hancock@neu.edu.
authors.forename: William S
authors.initials: WS
authors.lastname: Hancock
authors.affiliation: Bioinformatics and High-Throughput Analysis Laboratory, Seattle Children's Research Institute, Seattle, WA 98101, USA. egnklkr@gmail.com.|Data and Analytics, Seattle Children's Hospital, Seattle, WA 98101, USA. egnklkr@gmail.com.|Data-Enabled Life Sciences Alliance (DELSA), Seattle, WA 98101, USA. egnklkr@gmail.com.|Departments of Biomedical Informatics and Medical Education and Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA. egnklkr@gmail.com.
authors.forename: Eugene
authors.initials: E
authors.lastname: Kolker
authors.affiliation: Department of Biomedical Sciences, Macquarie University, Sydney NSW 2109, Australia. susan.fanayan@mq.edu.au.
authors.forename: Susan
authors.initials: S
authors.lastname: Fanayan
keywords: Daoy; SHH subtype; UW228; WNT subtype; medulloblastoma; proteome; transcriptome