Programmed cell death 6 interacting protein (PDCD6IP) and Rabenosyn-5 (ZFYVE20) are potential urinary biomarkers for upper gastrointestinal cancer

Holger Husi, Richard J E Skipworth, Andrew Cronshaw, Nathan A Stephens, Henning Wackerhage, Carolyn Greig, Kenneth C H Fearon, James A Ross

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

PURPOSE: Cancer of the upper digestive tract (uGI) is a major contributor to cancer-related death worldwide. Due to a rise in occurrence, together with poor survival rates and a lack of diagnostic or prognostic clinical assays, there is a clear need to establish molecular biomarkers.

EXPERIMENTAL DESIGN: Initial assessment was performed on urine samples from 60 control and 60 uGI cancer patients using MS to establish a peak pattern or fingerprint model, which was validated by a further set of 59 samples.

RESULTS: We detected 86 cluster peaks by MS above frequency and detection thresholds. Statistical testing and model building resulted in a peak profiling model of five relevant peaks with 88% overall sensitivity and 91% specificity, and overall correctness of 90%. High-resolution MS of 40 samples in the 2-10 kDa range resulted in 646 identified proteins, and pattern matching identified four of the five model peaks within significant parameters, namely programmed cell death 6 interacting protein (PDCD6IP/Alix/AIP1), Rabenosyn-5 (ZFYVE20), protein S100A8, and protein S100A9, of which the first two were validated by Western blotting.

CONCLUSIONS AND CLINICAL RELEVANCE: We demonstrate that MS analysis of human urine can identify lead biomarker candidates in uGI cancers, which makes this technique potentially useful in defining and consolidating biomarker patterns for uGI cancer screening.

Original languageEnglish
Pages (from-to)586-596
Number of pages11
JournalProteomics. Clinical applications
Volume9
Issue number5-6
Early online date8 May 2015
DOIs
Publication statusPublished - Jun 2015

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Gastrointestinal Neoplasms
Biomarkers
Cell death
Cell Death
Neoplasms
Calgranulin A
Proteins
Urine
Apoptosis Regulatory Proteins
Pattern matching
Dermatoglyphics
Statistical Models
Early Detection of Cancer
Gastrointestinal Tract
Assays
Screening
Survival Rate
Western Blotting
Sensitivity and Specificity
Testing

Keywords

  • mass spectrometry
  • upper gastrointestinal
  • urine biomarker

Cite this

Programmed cell death 6 interacting protein (PDCD6IP) and Rabenosyn-5 (ZFYVE20) are potential urinary biomarkers for upper gastrointestinal cancer. / Husi, Holger; Skipworth, Richard J E; Cronshaw, Andrew; Stephens, Nathan A; Wackerhage, Henning; Greig, Carolyn; Fearon, Kenneth C H; Ross, James A.

In: Proteomics. Clinical applications, Vol. 9, No. 5-6, 06.2015, p. 586-596.

Research output: Contribution to journalArticle

Husi, Holger ; Skipworth, Richard J E ; Cronshaw, Andrew ; Stephens, Nathan A ; Wackerhage, Henning ; Greig, Carolyn ; Fearon, Kenneth C H ; Ross, James A. / Programmed cell death 6 interacting protein (PDCD6IP) and Rabenosyn-5 (ZFYVE20) are potential urinary biomarkers for upper gastrointestinal cancer. In: Proteomics. Clinical applications. 2015 ; Vol. 9, No. 5-6. pp. 586-596.
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note = "{\circledC} 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Acknowledgment We thank J. Black for technical assistance with Western blotting. Funding of this work was provided by the University of Edinburgh. H.H. did the sample preparations, SELDI measurements, data analysis, MASCOT searches, software design and coding, and co-wrote the manuscript; N.S., C.G., and H.W. organized patient recruitment, sampling, and clinical analysis; A.C. did the LC-MS/MS measurements; R.S. and JR co-wrote the manuscript; J.R., K.F., H.H., and R.S. devised the study; and J.R. and K.F. supervised the research. The authors have declared no conflict of interest.",
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AU - Husi, Holger

AU - Skipworth, Richard J E

AU - Cronshaw, Andrew

AU - Stephens, Nathan A

AU - Wackerhage, Henning

AU - Greig, Carolyn

AU - Fearon, Kenneth C H

AU - Ross, James A

N1 - © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Acknowledgment We thank J. Black for technical assistance with Western blotting. Funding of this work was provided by the University of Edinburgh. H.H. did the sample preparations, SELDI measurements, data analysis, MASCOT searches, software design and coding, and co-wrote the manuscript; N.S., C.G., and H.W. organized patient recruitment, sampling, and clinical analysis; A.C. did the LC-MS/MS measurements; R.S. and JR co-wrote the manuscript; J.R., K.F., H.H., and R.S. devised the study; and J.R. and K.F. supervised the research. The authors have declared no conflict of interest.

PY - 2015/6

Y1 - 2015/6

N2 - PURPOSE: Cancer of the upper digestive tract (uGI) is a major contributor to cancer-related death worldwide. Due to a rise in occurrence, together with poor survival rates and a lack of diagnostic or prognostic clinical assays, there is a clear need to establish molecular biomarkers.EXPERIMENTAL DESIGN: Initial assessment was performed on urine samples from 60 control and 60 uGI cancer patients using MS to establish a peak pattern or fingerprint model, which was validated by a further set of 59 samples.RESULTS: We detected 86 cluster peaks by MS above frequency and detection thresholds. Statistical testing and model building resulted in a peak profiling model of five relevant peaks with 88% overall sensitivity and 91% specificity, and overall correctness of 90%. High-resolution MS of 40 samples in the 2-10 kDa range resulted in 646 identified proteins, and pattern matching identified four of the five model peaks within significant parameters, namely programmed cell death 6 interacting protein (PDCD6IP/Alix/AIP1), Rabenosyn-5 (ZFYVE20), protein S100A8, and protein S100A9, of which the first two were validated by Western blotting.CONCLUSIONS AND CLINICAL RELEVANCE: We demonstrate that MS analysis of human urine can identify lead biomarker candidates in uGI cancers, which makes this technique potentially useful in defining and consolidating biomarker patterns for uGI cancer screening.

AB - PURPOSE: Cancer of the upper digestive tract (uGI) is a major contributor to cancer-related death worldwide. Due to a rise in occurrence, together with poor survival rates and a lack of diagnostic or prognostic clinical assays, there is a clear need to establish molecular biomarkers.EXPERIMENTAL DESIGN: Initial assessment was performed on urine samples from 60 control and 60 uGI cancer patients using MS to establish a peak pattern or fingerprint model, which was validated by a further set of 59 samples.RESULTS: We detected 86 cluster peaks by MS above frequency and detection thresholds. Statistical testing and model building resulted in a peak profiling model of five relevant peaks with 88% overall sensitivity and 91% specificity, and overall correctness of 90%. High-resolution MS of 40 samples in the 2-10 kDa range resulted in 646 identified proteins, and pattern matching identified four of the five model peaks within significant parameters, namely programmed cell death 6 interacting protein (PDCD6IP/Alix/AIP1), Rabenosyn-5 (ZFYVE20), protein S100A8, and protein S100A9, of which the first two were validated by Western blotting.CONCLUSIONS AND CLINICAL RELEVANCE: We demonstrate that MS analysis of human urine can identify lead biomarker candidates in uGI cancers, which makes this technique potentially useful in defining and consolidating biomarker patterns for uGI cancer screening.

KW - mass spectrometry

KW - upper gastrointestinal

KW - urine biomarker

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JO - Proteomics. Clinical applications

JF - Proteomics. Clinical applications

SN - 1862-8354

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