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Proteomes 2017, 5(1), 5; doi:10.3390/proteomes5010005

Integrated Proteomic and Transcriptomic-Based Approaches to Identifying Signature Biomarkers and Pathways for Elucidation of Daoy and UW228 Subtypes

1
Bioinformatics and High-Throughput Analysis Laboratory, Seattle Children’s Research Institute, Seattle, WA 98101, USA
2
Data and Analytics, Seattle Children’s Hospital, Seattle, WA 98101, USA
3
Data-Enabled Life Sciences Alliance (DELSA), Seattle, WA 98101, USA
4
High-Throughput Analysis Core, Seattle Children’s Research Institute, Seattle, WA 98101, USA
5
Department of Chemistry and Biological Sciences, Macquarie University, Sydney 2109, Australia
6
Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA
7
Beijing Genomics Institute, Shenzhen 518083, Guangdong, China
8
Chinese Academy of Sciences, Beijing 100101, China
9
Department of Biomedical Sciences, Macquarie University, Sydney NSW 2109, Australia
10
Departments of Biomedical Informatics and Medical Education and Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Karl-Friedrich Becker and Jacek R. Wisniewski
Received: 15 November 2016 / Revised: 16 January 2017 / Accepted: 17 January 2017 / Published: 3 February 2017
(This article belongs to the Special Issue Cancer Proteomics)
View Full-Text   |   Download PDF [1808 KB, uploaded 6 February 2017]   |  

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. View Full-Text
Keywords: medulloblastoma; Daoy; UW228; SHH subtype; WNT subtype; transcriptome; proteome medulloblastoma; Daoy; UW228; SHH subtype; WNT subtype; transcriptome; proteome
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Higdon, R.; Kala, J.; Wilkins, D.; Yan, J.F.; Sethi, M.K.; Lin, L.; Liu, S.; Montague, E.; Janko, I.; Choiniere, J.; Kolker, N.; Hancock, W.S.; Kolker, E.; Fanayan, S. Integrated Proteomic and Transcriptomic-Based Approaches to Identifying Signature Biomarkers and Pathways for Elucidation of Daoy and UW228 Subtypes. Proteomes 2017, 5, 5.

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