Proteomic profiling of rectal cancer reveals acid ceramidase is implicated in radiation response

D. L. Bowden, P. A. Sutton, M. A. Wall, Puthen V. Jithesh, R. E. Jenkins, D. H. Palmer, C. E. Goldring, J. L. Parsons, B. K. Park, N. R. Kitteringham, D. Vimalachandran

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Neoadjuvant chemoradiotherapy (CRT) is used in locally advanced rectal cancer when tumours threaten the circumferential resection margin, with varying response to treatment. This experimental study aimed to identify significantly differentially expressed proteins between patients responding and not responding to CRT, and to validate any proteins of interest. Methods: Mass spectrometry (with isobaric tagging for relative quantification) analysis of rectal cancers pre- and post-CRT, and at resection. Validation of proteins of interest was performed by assessing tissue microarray (TMA) immunohistochemistry expression in a further 111 patients with rectal cancer. Results: Proteomic data are available via ProteomeXchange with identifier PXD008436. Reduced abundance of contributing peptide ions for acid ceramidase (AC) (log fold change −1.526, p = 1.17E−02) was observed in CRT responders. Differential expression of AC was confirmed upon analysis of the TMAs. Cancer site expression of AC in stromal cells from post-CRT resection specimens was observed to be relatively low in pathological complete response (p = 0.003), and relatively high with no response to CRT (p = 0.017). Conclusion: AC may be implicated in the response of rectal cancer to CRT. We propose its further assessment as a novel potential biomarker and therapeutic target. Significance: There is a need for biomarkers to guide the use of chemoradiotherapy in rectal cancer, as none are in routine clinical use. We have determined acid ceramidase may have a role in radiation response, based on novel proteomic profiling and validation in a wider dataset using tissue microarrays. The ability to predict or improve response would positively select those patients who will derive benefit, prevent delays in the local and systemic management of disease in non-responders, and reduce morbidity associated with chemoradiotherapy.

Original languageEnglish
Pages (from-to)53-60
Number of pages8
JournalJournal of Proteomics
Volume179
DOIs
Publication statusPublished - 15 May 2018

Fingerprint

Chemoradiotherapy
Acid Ceramidase
Rectal Neoplasms
Proteomics
Radiation
Biomarkers
Microarrays
Tissue
Proteins
Cathode ray tubes
Stromal Cells
Disease Management
Mass spectrometry
Tumors
Mass Spectrometry
Neoplasms

Keywords

  • Biomarker
  • Cancer
  • Chemoradiotherapy
  • Proteomics
  • Rectal
  • Response

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Cite this

Bowden, D. L., Sutton, P. A., Wall, M. A., Jithesh, P. V., Jenkins, R. E., Palmer, D. H., ... Vimalachandran, D. (2018). Proteomic profiling of rectal cancer reveals acid ceramidase is implicated in radiation response. Journal of Proteomics, 179, 53-60. https://doi.org/10.1016/j.jprot.2018.02.030

Proteomic profiling of rectal cancer reveals acid ceramidase is implicated in radiation response. / Bowden, D. L.; Sutton, P. A.; Wall, M. A.; Jithesh, Puthen V.; Jenkins, R. E.; Palmer, D. H.; Goldring, C. E.; Parsons, J. L.; Park, B. K.; Kitteringham, N. R.; Vimalachandran, D.

In: Journal of Proteomics, Vol. 179, 15.05.2018, p. 53-60.

Research output: Contribution to journalArticle

Bowden, DL, Sutton, PA, Wall, MA, Jithesh, PV, Jenkins, RE, Palmer, DH, Goldring, CE, Parsons, JL, Park, BK, Kitteringham, NR & Vimalachandran, D 2018, 'Proteomic profiling of rectal cancer reveals acid ceramidase is implicated in radiation response', Journal of Proteomics, vol. 179, pp. 53-60. https://doi.org/10.1016/j.jprot.2018.02.030
Bowden, D. L. ; Sutton, P. A. ; Wall, M. A. ; Jithesh, Puthen V. ; Jenkins, R. E. ; Palmer, D. H. ; Goldring, C. E. ; Parsons, J. L. ; Park, B. K. ; Kitteringham, N. R. ; Vimalachandran, D. / Proteomic profiling of rectal cancer reveals acid ceramidase is implicated in radiation response. In: Journal of Proteomics. 2018 ; Vol. 179. pp. 53-60.
@article{692e1310c84947b1a6ceb71b9cc8a543,
title = "Proteomic profiling of rectal cancer reveals acid ceramidase is implicated in radiation response",
abstract = "Background: Neoadjuvant chemoradiotherapy (CRT) is used in locally advanced rectal cancer when tumours threaten the circumferential resection margin, with varying response to treatment. This experimental study aimed to identify significantly differentially expressed proteins between patients responding and not responding to CRT, and to validate any proteins of interest. Methods: Mass spectrometry (with isobaric tagging for relative quantification) analysis of rectal cancers pre- and post-CRT, and at resection. Validation of proteins of interest was performed by assessing tissue microarray (TMA) immunohistochemistry expression in a further 111 patients with rectal cancer. Results: Proteomic data are available via ProteomeXchange with identifier PXD008436. Reduced abundance of contributing peptide ions for acid ceramidase (AC) (log fold change −1.526, p = 1.17E−02) was observed in CRT responders. Differential expression of AC was confirmed upon analysis of the TMAs. Cancer site expression of AC in stromal cells from post-CRT resection specimens was observed to be relatively low in pathological complete response (p = 0.003), and relatively high with no response to CRT (p = 0.017). Conclusion: AC may be implicated in the response of rectal cancer to CRT. We propose its further assessment as a novel potential biomarker and therapeutic target. Significance: There is a need for biomarkers to guide the use of chemoradiotherapy in rectal cancer, as none are in routine clinical use. We have determined acid ceramidase may have a role in radiation response, based on novel proteomic profiling and validation in a wider dataset using tissue microarrays. The ability to predict or improve response would positively select those patients who will derive benefit, prevent delays in the local and systemic management of disease in non-responders, and reduce morbidity associated with chemoradiotherapy.",
keywords = "Biomarker, Cancer, Chemoradiotherapy, Proteomics, Rectal, Response",
author = "Bowden, {D. L.} and Sutton, {P. A.} and Wall, {M. A.} and Jithesh, {Puthen V.} and Jenkins, {R. E.} and Palmer, {D. H.} and Goldring, {C. E.} and Parsons, {J. L.} and Park, {B. K.} and Kitteringham, {N. R.} and D. Vimalachandran",
year = "2018",
month = "5",
day = "15",
doi = "10.1016/j.jprot.2018.02.030",
language = "English",
volume = "179",
pages = "53--60",
journal = "Journal of Proteomics",
issn = "1874-3919",
publisher = "Elsevier",

}

TY - JOUR

T1 - Proteomic profiling of rectal cancer reveals acid ceramidase is implicated in radiation response

AU - Bowden, D. L.

AU - Sutton, P. A.

AU - Wall, M. A.

AU - Jithesh, Puthen V.

AU - Jenkins, R. E.

AU - Palmer, D. H.

AU - Goldring, C. E.

AU - Parsons, J. L.

AU - Park, B. K.

AU - Kitteringham, N. R.

AU - Vimalachandran, D.

PY - 2018/5/15

Y1 - 2018/5/15

N2 - Background: Neoadjuvant chemoradiotherapy (CRT) is used in locally advanced rectal cancer when tumours threaten the circumferential resection margin, with varying response to treatment. This experimental study aimed to identify significantly differentially expressed proteins between patients responding and not responding to CRT, and to validate any proteins of interest. Methods: Mass spectrometry (with isobaric tagging for relative quantification) analysis of rectal cancers pre- and post-CRT, and at resection. Validation of proteins of interest was performed by assessing tissue microarray (TMA) immunohistochemistry expression in a further 111 patients with rectal cancer. Results: Proteomic data are available via ProteomeXchange with identifier PXD008436. Reduced abundance of contributing peptide ions for acid ceramidase (AC) (log fold change −1.526, p = 1.17E−02) was observed in CRT responders. Differential expression of AC was confirmed upon analysis of the TMAs. Cancer site expression of AC in stromal cells from post-CRT resection specimens was observed to be relatively low in pathological complete response (p = 0.003), and relatively high with no response to CRT (p = 0.017). Conclusion: AC may be implicated in the response of rectal cancer to CRT. We propose its further assessment as a novel potential biomarker and therapeutic target. Significance: There is a need for biomarkers to guide the use of chemoradiotherapy in rectal cancer, as none are in routine clinical use. We have determined acid ceramidase may have a role in radiation response, based on novel proteomic profiling and validation in a wider dataset using tissue microarrays. The ability to predict or improve response would positively select those patients who will derive benefit, prevent delays in the local and systemic management of disease in non-responders, and reduce morbidity associated with chemoradiotherapy.

AB - Background: Neoadjuvant chemoradiotherapy (CRT) is used in locally advanced rectal cancer when tumours threaten the circumferential resection margin, with varying response to treatment. This experimental study aimed to identify significantly differentially expressed proteins between patients responding and not responding to CRT, and to validate any proteins of interest. Methods: Mass spectrometry (with isobaric tagging for relative quantification) analysis of rectal cancers pre- and post-CRT, and at resection. Validation of proteins of interest was performed by assessing tissue microarray (TMA) immunohistochemistry expression in a further 111 patients with rectal cancer. Results: Proteomic data are available via ProteomeXchange with identifier PXD008436. Reduced abundance of contributing peptide ions for acid ceramidase (AC) (log fold change −1.526, p = 1.17E−02) was observed in CRT responders. Differential expression of AC was confirmed upon analysis of the TMAs. Cancer site expression of AC in stromal cells from post-CRT resection specimens was observed to be relatively low in pathological complete response (p = 0.003), and relatively high with no response to CRT (p = 0.017). Conclusion: AC may be implicated in the response of rectal cancer to CRT. We propose its further assessment as a novel potential biomarker and therapeutic target. Significance: There is a need for biomarkers to guide the use of chemoradiotherapy in rectal cancer, as none are in routine clinical use. We have determined acid ceramidase may have a role in radiation response, based on novel proteomic profiling and validation in a wider dataset using tissue microarrays. The ability to predict or improve response would positively select those patients who will derive benefit, prevent delays in the local and systemic management of disease in non-responders, and reduce morbidity associated with chemoradiotherapy.

KW - Biomarker

KW - Cancer

KW - Chemoradiotherapy

KW - Proteomics

KW - Rectal

KW - Response

UR - http://www.scopus.com/inward/record.url?scp=85044596111&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044596111&partnerID=8YFLogxK

U2 - 10.1016/j.jprot.2018.02.030

DO - 10.1016/j.jprot.2018.02.030

M3 - Article

VL - 179

SP - 53

EP - 60

JO - Journal of Proteomics

JF - Journal of Proteomics

SN - 1874-3919

ER -