Tumour-educated circulating monocytes are powerful candidate biomarkers for diagnosis and disease follow-up of colorectal cancer

Alexander Hamm, Hans Prenen, Wouter Van Delm, Mario Di Matteo, Mathias Wenes, Estelle Delamarre, Thomas Schmidt, Jürgen Weitz, Roberta Sarmiento, Angelo Dezi, Giampietro Gasparini, Françoise Rothé, Robin Schmitz, André D'Hoore, Hannes Iserentant, Alain Hendlisz, Massimiliano Mazzone

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Objective Cancer immunology is a growing field of research whose aim is to develop innovative therapies and diagnostic tests. Starting from the hypothesis that immune cells promptly respond to harmful stimuli, we used peripheral blood monocytes in order to characterise a distinct gene expression profile and to evaluate its potential as a candidate diagnostic biomarker in patients with colorectal cancer (CRC), a still unmet clinical need. Design We performed a case-control study including 360 peripheral blood monocyte samples from four European oncological centres and defined a gene expression profile specific to CRC. The robustness of the genetic profile and disease specificity were assessed in an independent setting. Results This screen returned 43 putative diagnostic markers, which we refined and validated in the confirmative multicentric analysis to 23 genes with outstanding diagnostic accuracy (area under the curve (AUC)=0.99 (0.99 to 1.00), Se=100.0% (100.0% to 100.0%), Sp=92.9% (78.6% to 100.0%) in multiple-gene receiver operating characteristic analysis). The diagnostic accuracy was robustly maintained in prospectively collected independent samples (AUC=0.95 (0.85 to 1.00), Se=92.6% (81.5% to 100.0%), Sp=92.3% (76.9% to 100.0%). This monocyte signature was expressed at early disease onset, remained robust over the course of disease progression, and was specific for the monocytic fraction of mononuclear cells. The gene modulation was induced specifically by soluble factors derived from transformed colon epithelium in comparison to normal colon or other cancer histotypes. Moreover, expression changes were plastic and reversible, as they were abrogated upon withdrawal of these tumour-released factors. Consistently, the modified set of genes reverted to normal expression upon curative treatment and was specific for CRC. Conclusions Our study is the first to demonstrate monocyte plasticity in response to tumour-released soluble factors. The identified distinct signature in tumour-educated monocytes might be used as a candidate biomarker in CRC diagnosis and harbours the potential for disease follow-up and therapeutic monitoring.

Original languageEnglish
JournalGut
DOIs
Publication statusAccepted/In press - Mar 26 2015

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Monocytes
Colorectal Neoplasms
Biomarkers
Neoplasms
Transcriptome
Genes
Area Under Curve
Colon
Investigational Therapies
Inborn Genetic Diseases
Allergy and Immunology
Routine Diagnostic Tests
ROC Curve
Plastics
Disease Progression
Case-Control Studies
Epithelium
Therapeutics
Research

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Hamm, A., Prenen, H., Delm, W. V., Matteo, M. D., Wenes, M., Delamarre, E., ... Mazzone, M. (Accepted/In press). Tumour-educated circulating monocytes are powerful candidate biomarkers for diagnosis and disease follow-up of colorectal cancer. Gut. https://doi.org/10.1136/gutjnl-2014-308988

Tumour-educated circulating monocytes are powerful candidate biomarkers for diagnosis and disease follow-up of colorectal cancer. / Hamm, Alexander; Prenen, Hans; Delm, Wouter Van; Matteo, Mario Di; Wenes, Mathias; Delamarre, Estelle; Schmidt, Thomas; Weitz, Jürgen; Sarmiento, Roberta; Dezi, Angelo; Gasparini, Giampietro; Rothé, Françoise; Schmitz, Robin; D'Hoore, André; Iserentant, Hannes; Hendlisz, Alain; Mazzone, Massimiliano.

In: Gut, 26.03.2015.

Research output: Contribution to journalArticle

Hamm, A, Prenen, H, Delm, WV, Matteo, MD, Wenes, M, Delamarre, E, Schmidt, T, Weitz, J, Sarmiento, R, Dezi, A, Gasparini, G, Rothé, F, Schmitz, R, D'Hoore, A, Iserentant, H, Hendlisz, A & Mazzone, M 2015, 'Tumour-educated circulating monocytes are powerful candidate biomarkers for diagnosis and disease follow-up of colorectal cancer', Gut. https://doi.org/10.1136/gutjnl-2014-308988
Hamm, Alexander ; Prenen, Hans ; Delm, Wouter Van ; Matteo, Mario Di ; Wenes, Mathias ; Delamarre, Estelle ; Schmidt, Thomas ; Weitz, Jürgen ; Sarmiento, Roberta ; Dezi, Angelo ; Gasparini, Giampietro ; Rothé, Françoise ; Schmitz, Robin ; D'Hoore, André ; Iserentant, Hannes ; Hendlisz, Alain ; Mazzone, Massimiliano. / Tumour-educated circulating monocytes are powerful candidate biomarkers for diagnosis and disease follow-up of colorectal cancer. In: Gut. 2015.
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abstract = "Objective Cancer immunology is a growing field of research whose aim is to develop innovative therapies and diagnostic tests. Starting from the hypothesis that immune cells promptly respond to harmful stimuli, we used peripheral blood monocytes in order to characterise a distinct gene expression profile and to evaluate its potential as a candidate diagnostic biomarker in patients with colorectal cancer (CRC), a still unmet clinical need. Design We performed a case-control study including 360 peripheral blood monocyte samples from four European oncological centres and defined a gene expression profile specific to CRC. The robustness of the genetic profile and disease specificity were assessed in an independent setting. Results This screen returned 43 putative diagnostic markers, which we refined and validated in the confirmative multicentric analysis to 23 genes with outstanding diagnostic accuracy (area under the curve (AUC)=0.99 (0.99 to 1.00), Se=100.0{\%} (100.0{\%} to 100.0{\%}), Sp=92.9{\%} (78.6{\%} to 100.0{\%}) in multiple-gene receiver operating characteristic analysis). The diagnostic accuracy was robustly maintained in prospectively collected independent samples (AUC=0.95 (0.85 to 1.00), Se=92.6{\%} (81.5{\%} to 100.0{\%}), Sp=92.3{\%} (76.9{\%} to 100.0{\%}). This monocyte signature was expressed at early disease onset, remained robust over the course of disease progression, and was specific for the monocytic fraction of mononuclear cells. The gene modulation was induced specifically by soluble factors derived from transformed colon epithelium in comparison to normal colon or other cancer histotypes. Moreover, expression changes were plastic and reversible, as they were abrogated upon withdrawal of these tumour-released factors. Consistently, the modified set of genes reverted to normal expression upon curative treatment and was specific for CRC. Conclusions Our study is the first to demonstrate monocyte plasticity in response to tumour-released soluble factors. The identified distinct signature in tumour-educated monocytes might be used as a candidate biomarker in CRC diagnosis and harbours the potential for disease follow-up and therapeutic monitoring.",
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T1 - Tumour-educated circulating monocytes are powerful candidate biomarkers for diagnosis and disease follow-up of colorectal cancer

AU - Hamm, Alexander

AU - Prenen, Hans

AU - Delm, Wouter Van

AU - Matteo, Mario Di

AU - Wenes, Mathias

AU - Delamarre, Estelle

AU - Schmidt, Thomas

AU - Weitz, Jürgen

AU - Sarmiento, Roberta

AU - Dezi, Angelo

AU - Gasparini, Giampietro

AU - Rothé, Françoise

AU - Schmitz, Robin

AU - D'Hoore, André

AU - Iserentant, Hannes

AU - Hendlisz, Alain

AU - Mazzone, Massimiliano

PY - 2015/3/26

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N2 - Objective Cancer immunology is a growing field of research whose aim is to develop innovative therapies and diagnostic tests. Starting from the hypothesis that immune cells promptly respond to harmful stimuli, we used peripheral blood monocytes in order to characterise a distinct gene expression profile and to evaluate its potential as a candidate diagnostic biomarker in patients with colorectal cancer (CRC), a still unmet clinical need. Design We performed a case-control study including 360 peripheral blood monocyte samples from four European oncological centres and defined a gene expression profile specific to CRC. The robustness of the genetic profile and disease specificity were assessed in an independent setting. Results This screen returned 43 putative diagnostic markers, which we refined and validated in the confirmative multicentric analysis to 23 genes with outstanding diagnostic accuracy (area under the curve (AUC)=0.99 (0.99 to 1.00), Se=100.0% (100.0% to 100.0%), Sp=92.9% (78.6% to 100.0%) in multiple-gene receiver operating characteristic analysis). The diagnostic accuracy was robustly maintained in prospectively collected independent samples (AUC=0.95 (0.85 to 1.00), Se=92.6% (81.5% to 100.0%), Sp=92.3% (76.9% to 100.0%). This monocyte signature was expressed at early disease onset, remained robust over the course of disease progression, and was specific for the monocytic fraction of mononuclear cells. The gene modulation was induced specifically by soluble factors derived from transformed colon epithelium in comparison to normal colon or other cancer histotypes. Moreover, expression changes were plastic and reversible, as they were abrogated upon withdrawal of these tumour-released factors. Consistently, the modified set of genes reverted to normal expression upon curative treatment and was specific for CRC. Conclusions Our study is the first to demonstrate monocyte plasticity in response to tumour-released soluble factors. The identified distinct signature in tumour-educated monocytes might be used as a candidate biomarker in CRC diagnosis and harbours the potential for disease follow-up and therapeutic monitoring.

AB - Objective Cancer immunology is a growing field of research whose aim is to develop innovative therapies and diagnostic tests. Starting from the hypothesis that immune cells promptly respond to harmful stimuli, we used peripheral blood monocytes in order to characterise a distinct gene expression profile and to evaluate its potential as a candidate diagnostic biomarker in patients with colorectal cancer (CRC), a still unmet clinical need. Design We performed a case-control study including 360 peripheral blood monocyte samples from four European oncological centres and defined a gene expression profile specific to CRC. The robustness of the genetic profile and disease specificity were assessed in an independent setting. Results This screen returned 43 putative diagnostic markers, which we refined and validated in the confirmative multicentric analysis to 23 genes with outstanding diagnostic accuracy (area under the curve (AUC)=0.99 (0.99 to 1.00), Se=100.0% (100.0% to 100.0%), Sp=92.9% (78.6% to 100.0%) in multiple-gene receiver operating characteristic analysis). The diagnostic accuracy was robustly maintained in prospectively collected independent samples (AUC=0.95 (0.85 to 1.00), Se=92.6% (81.5% to 100.0%), Sp=92.3% (76.9% to 100.0%). This monocyte signature was expressed at early disease onset, remained robust over the course of disease progression, and was specific for the monocytic fraction of mononuclear cells. The gene modulation was induced specifically by soluble factors derived from transformed colon epithelium in comparison to normal colon or other cancer histotypes. Moreover, expression changes were plastic and reversible, as they were abrogated upon withdrawal of these tumour-released factors. Consistently, the modified set of genes reverted to normal expression upon curative treatment and was specific for CRC. Conclusions Our study is the first to demonstrate monocyte plasticity in response to tumour-released soluble factors. The identified distinct signature in tumour-educated monocytes might be used as a candidate biomarker in CRC diagnosis and harbours the potential for disease follow-up and therapeutic monitoring.

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