Proteomic characterization of primary diffuse large B-cell lymphomas in the central nervous system: Laboratory investigation

Jie Li, Hiroaki Okamoto, Chunyue Yin, Jay Jagannathan, Jun Takizawa, Sadao Aoki, Sven Gläsker, Elisabeth J. Rushing, Alexander Vortmeyer, Edward H. Oldfield, Ryuya Yamanaka, Zhengping Zhuang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Object. The lack of primary lymphoid tissue within the central nervous system (CNS) confounds our understanding of the pathogenesis of primary CNS lymphomas (PCNSLs). Comparing the protein expression of PCNSLs and sporadic systemic lymphomas (SSLs) provides a useful strategy for identifying a molecular signature that characterizes disease-associated features and provides information regarding tumor initiation and progression. Methods. Seven diffuse large B-cell PCNSLs were selected to undergo 2D gel electrophoresis, and profiled proteomes from these PCNSLs were compared with those from 7 diffuse large B-cell SSLs. Distinguishing proteins were sequenced using mass spectrometry. Results. Two-dimensional gel electrophoresis identified an average of 706 proteins from each specimen. Computerized gel analysis and manual reconfirmation revealed a 96% similarity in the proteomes of PCNSLs and SSLs. Comparative analysis identified 9 proteins significantly overexpressed (p < 0.05) and 16 proteins downregulated in PCNSLs. The proteomic findings were further validated using Western blot and immunohistochemical staining. Conclusions. The similarities in proteomic patterns between PCNSLs and SSLs suggest that these tumor types share structural similarities, acquired during differentiation. The ultimate fate of lymphomatous cells (CNS vs systemic) may be related to differentially expressed proteins, which function in homing and host processing. Elucidating the roles of these differentially expressed proteins will prove valuable in understanding the pathogenesis of PCNSL.

Original languageEnglish (US)
Pages (from-to)536-546
Number of pages11
JournalJournal of neurosurgery
Volume109
Issue number3
DOIs
StatePublished - Sep 1 2008
Externally publishedYes

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Proteomics
Lymphoma
Central Nervous System
Proteins
Electrophoresis, Gel, Two-Dimensional
Proteome
B-Lymphocytes
Lymphoid Tissue
Mass Spectrometry
Neoplasms
Down-Regulation
Western Blotting
Gels

Keywords

  • B-cell lymphoma
  • Gel electrophoresis
  • Proteomics
  • Sporadic systemic lymphoma
  • Western blot

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Proteomic characterization of primary diffuse large B-cell lymphomas in the central nervous system : Laboratory investigation. / Li, Jie; Okamoto, Hiroaki; Yin, Chunyue; Jagannathan, Jay; Takizawa, Jun; Aoki, Sadao; Gläsker, Sven; Rushing, Elisabeth J.; Vortmeyer, Alexander; Oldfield, Edward H.; Yamanaka, Ryuya; Zhuang, Zhengping.

In: Journal of neurosurgery, Vol. 109, No. 3, 01.09.2008, p. 536-546.

Research output: Contribution to journalArticle

Li, J, Okamoto, H, Yin, C, Jagannathan, J, Takizawa, J, Aoki, S, Gläsker, S, Rushing, EJ, Vortmeyer, A, Oldfield, EH, Yamanaka, R & Zhuang, Z 2008, 'Proteomic characterization of primary diffuse large B-cell lymphomas in the central nervous system: Laboratory investigation', Journal of neurosurgery, vol. 109, no. 3, pp. 536-546. https://doi.org/10.3171/JNS/2008/109/9/0536
Li, Jie ; Okamoto, Hiroaki ; Yin, Chunyue ; Jagannathan, Jay ; Takizawa, Jun ; Aoki, Sadao ; Gläsker, Sven ; Rushing, Elisabeth J. ; Vortmeyer, Alexander ; Oldfield, Edward H. ; Yamanaka, Ryuya ; Zhuang, Zhengping. / Proteomic characterization of primary diffuse large B-cell lymphomas in the central nervous system : Laboratory investigation. In: Journal of neurosurgery. 2008 ; Vol. 109, No. 3. pp. 536-546.
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abstract = "Object. The lack of primary lymphoid tissue within the central nervous system (CNS) confounds our understanding of the pathogenesis of primary CNS lymphomas (PCNSLs). Comparing the protein expression of PCNSLs and sporadic systemic lymphomas (SSLs) provides a useful strategy for identifying a molecular signature that characterizes disease-associated features and provides information regarding tumor initiation and progression. Methods. Seven diffuse large B-cell PCNSLs were selected to undergo 2D gel electrophoresis, and profiled proteomes from these PCNSLs were compared with those from 7 diffuse large B-cell SSLs. Distinguishing proteins were sequenced using mass spectrometry. Results. Two-dimensional gel electrophoresis identified an average of 706 proteins from each specimen. Computerized gel analysis and manual reconfirmation revealed a 96{\%} similarity in the proteomes of PCNSLs and SSLs. Comparative analysis identified 9 proteins significantly overexpressed (p < 0.05) and 16 proteins downregulated in PCNSLs. The proteomic findings were further validated using Western blot and immunohistochemical staining. Conclusions. The similarities in proteomic patterns between PCNSLs and SSLs suggest that these tumor types share structural similarities, acquired during differentiation. The ultimate fate of lymphomatous cells (CNS vs systemic) may be related to differentially expressed proteins, which function in homing and host processing. Elucidating the roles of these differentially expressed proteins will prove valuable in understanding the pathogenesis of PCNSL.",
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AU - Li, Jie

AU - Okamoto, Hiroaki

AU - Yin, Chunyue

AU - Jagannathan, Jay

AU - Takizawa, Jun

AU - Aoki, Sadao

AU - Gläsker, Sven

AU - Rushing, Elisabeth J.

AU - Vortmeyer, Alexander

AU - Oldfield, Edward H.

AU - Yamanaka, Ryuya

AU - Zhuang, Zhengping

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N2 - Object. The lack of primary lymphoid tissue within the central nervous system (CNS) confounds our understanding of the pathogenesis of primary CNS lymphomas (PCNSLs). Comparing the protein expression of PCNSLs and sporadic systemic lymphomas (SSLs) provides a useful strategy for identifying a molecular signature that characterizes disease-associated features and provides information regarding tumor initiation and progression. Methods. Seven diffuse large B-cell PCNSLs were selected to undergo 2D gel electrophoresis, and profiled proteomes from these PCNSLs were compared with those from 7 diffuse large B-cell SSLs. Distinguishing proteins were sequenced using mass spectrometry. Results. Two-dimensional gel electrophoresis identified an average of 706 proteins from each specimen. Computerized gel analysis and manual reconfirmation revealed a 96% similarity in the proteomes of PCNSLs and SSLs. Comparative analysis identified 9 proteins significantly overexpressed (p < 0.05) and 16 proteins downregulated in PCNSLs. The proteomic findings were further validated using Western blot and immunohistochemical staining. Conclusions. The similarities in proteomic patterns between PCNSLs and SSLs suggest that these tumor types share structural similarities, acquired during differentiation. The ultimate fate of lymphomatous cells (CNS vs systemic) may be related to differentially expressed proteins, which function in homing and host processing. Elucidating the roles of these differentially expressed proteins will prove valuable in understanding the pathogenesis of PCNSL.

AB - Object. The lack of primary lymphoid tissue within the central nervous system (CNS) confounds our understanding of the pathogenesis of primary CNS lymphomas (PCNSLs). Comparing the protein expression of PCNSLs and sporadic systemic lymphomas (SSLs) provides a useful strategy for identifying a molecular signature that characterizes disease-associated features and provides information regarding tumor initiation and progression. Methods. Seven diffuse large B-cell PCNSLs were selected to undergo 2D gel electrophoresis, and profiled proteomes from these PCNSLs were compared with those from 7 diffuse large B-cell SSLs. Distinguishing proteins were sequenced using mass spectrometry. Results. Two-dimensional gel electrophoresis identified an average of 706 proteins from each specimen. Computerized gel analysis and manual reconfirmation revealed a 96% similarity in the proteomes of PCNSLs and SSLs. Comparative analysis identified 9 proteins significantly overexpressed (p < 0.05) and 16 proteins downregulated in PCNSLs. The proteomic findings were further validated using Western blot and immunohistochemical staining. Conclusions. The similarities in proteomic patterns between PCNSLs and SSLs suggest that these tumor types share structural similarities, acquired during differentiation. The ultimate fate of lymphomatous cells (CNS vs systemic) may be related to differentially expressed proteins, which function in homing and host processing. Elucidating the roles of these differentially expressed proteins will prove valuable in understanding the pathogenesis of PCNSL.

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