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Direct cancer tissue proteomics: a method to identify candidate cancer biomarkers from formalin-fixed paraffin-embedded archival tissues

Oncogene volume 26, pages 65–76 (2007)Cite this article

Abstract

Successful treatment of multiple cancer types requires early detection and identification of reliable biomarkers present in specific cancer tissues. To test the feasibility of identifying proteins from archival cancer tissues, we have developed a methodology, termed direct tissue proteomics (DTP), which can be used to identify proteins directly from formalin-fixed paraffin-embedded prostate cancer tissue samples. Using minute prostate biopsy sections, we demonstrate the identification of 428 prostate-expressed proteins using the shotgun method. Because the DTP method is not quantitative, we employed the absolute quantification method and demonstrate picogram level quantification of prostate-specific antigen. In depth bioinformatics analysis of these expressed proteins affords the categorization of metabolic pathways that may be important for distinct stages of prostate carcinogenesis. Furthermore, we validate Wnt-3 as an upregulated protein in cancerous prostate cells by immunohistochemistry. We propose that this general strategy provides a roadmap for successful identification of critical molecular targets of multiple cancer types.

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Abbreviations

DTP:

direct tissue proteomic

fmol:

femptomole

pg:

picogram

LC–MS/MS:

liquid chromatography–tandem mass spectrometry

TCA cycle:

tricarboxylic acid cycle

MALDI–TOF-MS:

matrix-assisted laser desorption ionization-time-of-flight mass spectrometry

SELDI–TOF:

surface-enhanced laser desorption ionization mass spectrometry

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Acknowledgements

We thank Michael Fong for his expert assistance in graphics and tables, and members of Han Lab for helpful discussion. This work was supported by R01 HL 67569, P01 HL70694, RR019436, funds from Neag Comprehensive Cancer Center and UConn Cancer Golf Proceeds.

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Author notes

  1. S-I Hwang and J Thumar: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cell Biology, Center for Vascular Biology, University of Connecticut School of Medicine, Farmington, CT, USA

    S-I Hwang, J Thumar, D H Lundgren, K Rezaul, V Mayya, L Wu & D K Han

  2. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    J Eng

  3. University of California Davis Genome Center, Davis, CA, USA

    M E Wright

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  1. S-I Hwang
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  2. J Thumar
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Correspondence to D K Han.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Hwang, SI., Thumar, J., Lundgren, D. et al. Direct cancer tissue proteomics: a method to identify candidate cancer biomarkers from formalin-fixed paraffin-embedded archival tissues. Oncogene 26, 65–76 (2007). https://doi.org/10.1038/sj.onc.1209755

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