Development and independent validation of a prognostic assay for stage ii colon cancer using formalin-fixed paraffin-embedded tissue

Richard D. Kennedy; Max Bylesjo; Peter Kerr; Timothy Davison; Julie M. Black; Elaine W. Kay; Robert J. Holt; Vitali Proutski; Miika Ahdesmaki; Vadim Farztdinov; Nicolas Goffard; Peter Hey; Fionnuala McDyer; Karl Mulligan; Julie Mussen; Eamonn O'Brien; Gavin Oliver; Steven M. Walker; Jude M. Mulligan; Claire Wilson; Andreas Winter; Diarmuid O'Donoghue; Hugh Mulcahy; Jacintha O'Sullivan; Kieran Sheahan; John Hyland; Rajiv Dhir; Oliver F. Bathe; Ola Winqvist; Upender Manne; Chandrakumar Shanmugam; Sridhar Ramaswamy; Eduardo J. Leon; William I. Smith; Ultan McDermott; Richard H. Wilson; Daniel Longley; John Marshall; Robert Cummins; Daniel J. Sargent; Patrick G. Johnston; D. Paul Harkin

doi:10.1200/JCO.2011.35.4498

Development and independent validation of a prognostic assay for stage ii colon cancer using formalin-fixed paraffin-embedded tissue

Richard D. Kennedy, Max Bylesjo, Peter Kerr, Timothy Davison, Julie M. Black, Elaine W. Kay, Robert J. Holt, Vitali Proutski, Miika Ahdesmaki, Vadim Farztdinov, Nicolas Goffard, Peter Hey, Fionnuala McDyer, Karl Mulligan, Julie Mussen, Eamonn O'Brien, Gavin Oliver, Steven M. Walker, Jude M. Mulligan, Claire WilsonAndreas Winter, Diarmuid O'Donoghue, Hugh Mulcahy, Jacintha O'Sullivan, Kieran Sheahan, John Hyland, Rajiv Dhir, Oliver F. Bathe, Ola Winqvist, Upender Manne, Chandrakumar Shanmugam, Sridhar Ramaswamy, Eduardo J. Leon, William I. Smith, Ultan McDermott, Richard H. Wilson, Daniel Longley, John Marshall, Robert Cummins, Daniel J. Sargent, Patrick G. Johnston, D. Paul Harkin

Quantitative Health Sciences

Research output: Contribution to journal › Article › peer-review

134 Scopus citations

Abstract

Purpose: Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray-based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples. Patients and Methods: A gene signature was developed from a balanced set of 73 patients with recurrent disease (high risk) and 142 patients with no recurrence (low risk) within 5 years of surgery. Results: The 634-probe set signature identified high-risk patients with a hazard ratio (HR) of 2.62 (P < .001) during cross validation of the training set. In an independent validation set of 144 samples, the signature identified high-risk patients with an HR of 2.53 (P < .001) for recurrence and an HR of 2.21 (P = .0084) for cancer-related death. Additionally, the signature was shown to perform independently from known prognostic factors (P < .001). Conclusion: This gene signature represents a novel prognostic biomarker for patients with stage II colon cancer that can be applied to FFPE tumor samples.

Original language	English (US)
Pages (from-to)	4620-4626
Number of pages	7
Journal	Journal of Clinical Oncology
Volume	29
Issue number	35
DOIs	https://doi.org/10.1200/JCO.2011.35.4498
State	Published - Dec 10 2011

ASJC Scopus subject areas

Oncology
Cancer Research

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Kennedy, R. D., Bylesjo, M., Kerr, P., Davison, T., Black, J. M., Kay, E. W., Holt, R. J., Proutski, V., Ahdesmaki, M., Farztdinov, V., Goffard, N., Hey, P., McDyer, F., Mulligan, K., Mussen, J., O'Brien, E., Oliver, G., Walker, S. M., Mulligan, J. M., ... Harkin, D. P. (2011). Development and independent validation of a prognostic assay for stage ii colon cancer using formalin-fixed paraffin-embedded tissue. Journal of Clinical Oncology, 29(35), 4620-4626. https://doi.org/10.1200/JCO.2011.35.4498

Kennedy, RD, Bylesjo, M, Kerr, P, Davison, T, Black, JM, Kay, EW, Holt, RJ, Proutski, V, Ahdesmaki, M, Farztdinov, V, Goffard, N, Hey, P, McDyer, F, Mulligan, K, Mussen, J, O'Brien, E, Oliver, G, Walker, SM, Mulligan, JM, Wilson, C, Winter, A, O'Donoghue, D, Mulcahy, H, O'Sullivan, J, Sheahan, K, Hyland, J, Dhir, R, Bathe, OF, Winqvist, O, Manne, U, Shanmugam, C, Ramaswamy, S, Leon, EJ, Smith, WI, McDermott, U, Wilson, RH, Longley, D, Marshall, J, Cummins, R, Sargent, DJ, Johnston, PG & Harkin, DP 2011, 'Development and independent validation of a prognostic assay for stage ii colon cancer using formalin-fixed paraffin-embedded tissue', Journal of Clinical Oncology, vol. 29, no. 35, pp. 4620-4626. https://doi.org/10.1200/JCO.2011.35.4498

@article{4a47547667434771a54782b0986e2893,

title = "Development and independent validation of a prognostic assay for stage ii colon cancer using formalin-fixed paraffin-embedded tissue",

abstract = "Purpose: Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray-based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples. Patients and Methods: A gene signature was developed from a balanced set of 73 patients with recurrent disease (high risk) and 142 patients with no recurrence (low risk) within 5 years of surgery. Results: The 634-probe set signature identified high-risk patients with a hazard ratio (HR) of 2.62 (P < .001) during cross validation of the training set. In an independent validation set of 144 samples, the signature identified high-risk patients with an HR of 2.53 (P < .001) for recurrence and an HR of 2.21 (P = .0084) for cancer-related death. Additionally, the signature was shown to perform independently from known prognostic factors (P < .001). Conclusion: This gene signature represents a novel prognostic biomarker for patients with stage II colon cancer that can be applied to FFPE tumor samples.",

author = "Kennedy, {Richard D.} and Max Bylesjo and Peter Kerr and Timothy Davison and Black, {Julie M.} and Kay, {Elaine W.} and Holt, {Robert J.} and Vitali Proutski and Miika Ahdesmaki and Vadim Farztdinov and Nicolas Goffard and Peter Hey and Fionnuala McDyer and Karl Mulligan and Julie Mussen and Eamonn O'Brien and Gavin Oliver and Walker, {Steven M.} and Mulligan, {Jude M.} and Claire Wilson and Andreas Winter and Diarmuid O'Donoghue and Hugh Mulcahy and Jacintha O'Sullivan and Kieran Sheahan and John Hyland and Rajiv Dhir and Bathe, {Oliver F.} and Ola Winqvist and Upender Manne and Chandrakumar Shanmugam and Sridhar Ramaswamy and Leon, {Eduardo J.} and Smith, {William I.} and Ultan McDermott and Wilson, {Richard H.} and Daniel Longley and John Marshall and Robert Cummins and Sargent, {Daniel J.} and Johnston, {Patrick G.} and Harkin, {D. Paul}",

year = "2011",

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doi = "10.1200/JCO.2011.35.4498",

language = "English (US)",

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pages = "4620--4626",

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T1 - Development and independent validation of a prognostic assay for stage ii colon cancer using formalin-fixed paraffin-embedded tissue

AU - Kennedy, Richard D.

AU - Bylesjo, Max

AU - Kerr, Peter

AU - Davison, Timothy

AU - Black, Julie M.

AU - Kay, Elaine W.

AU - Holt, Robert J.

AU - Proutski, Vitali

AU - Ahdesmaki, Miika

AU - Farztdinov, Vadim

AU - Goffard, Nicolas

AU - Hey, Peter

AU - McDyer, Fionnuala

AU - Mulligan, Karl

AU - Mussen, Julie

AU - O'Brien, Eamonn

AU - Oliver, Gavin

AU - Walker, Steven M.

AU - Mulligan, Jude M.

AU - Wilson, Claire

AU - Winter, Andreas

AU - O'Donoghue, Diarmuid

AU - Mulcahy, Hugh

AU - O'Sullivan, Jacintha

AU - Sheahan, Kieran

AU - Hyland, John

AU - Dhir, Rajiv

AU - Bathe, Oliver F.

AU - Winqvist, Ola

AU - Manne, Upender

AU - Shanmugam, Chandrakumar

AU - Ramaswamy, Sridhar

AU - Leon, Eduardo J.

AU - Smith, William I.

AU - McDermott, Ultan

AU - Wilson, Richard H.

AU - Longley, Daniel

AU - Marshall, John

AU - Cummins, Robert

AU - Sargent, Daniel J.

AU - Johnston, Patrick G.

AU - Harkin, D. Paul

PY - 2011/12/10

Y1 - 2011/12/10

N2 - Purpose: Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray-based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples. Patients and Methods: A gene signature was developed from a balanced set of 73 patients with recurrent disease (high risk) and 142 patients with no recurrence (low risk) within 5 years of surgery. Results: The 634-probe set signature identified high-risk patients with a hazard ratio (HR) of 2.62 (P < .001) during cross validation of the training set. In an independent validation set of 144 samples, the signature identified high-risk patients with an HR of 2.53 (P < .001) for recurrence and an HR of 2.21 (P = .0084) for cancer-related death. Additionally, the signature was shown to perform independently from known prognostic factors (P < .001). Conclusion: This gene signature represents a novel prognostic biomarker for patients with stage II colon cancer that can be applied to FFPE tumor samples.

AB - Purpose: Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray-based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples. Patients and Methods: A gene signature was developed from a balanced set of 73 patients with recurrent disease (high risk) and 142 patients with no recurrence (low risk) within 5 years of surgery. Results: The 634-probe set signature identified high-risk patients with a hazard ratio (HR) of 2.62 (P < .001) during cross validation of the training set. In an independent validation set of 144 samples, the signature identified high-risk patients with an HR of 2.53 (P < .001) for recurrence and an HR of 2.21 (P = .0084) for cancer-related death. Additionally, the signature was shown to perform independently from known prognostic factors (P < .001). Conclusion: This gene signature represents a novel prognostic biomarker for patients with stage II colon cancer that can be applied to FFPE tumor samples.

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AN - SCOPUS:83355174077

SN - 0732-183X

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EP - 4626

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 35

ER -

Development and independent validation of a prognostic assay for stage ii colon cancer using formalin-fixed paraffin-embedded tissue

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