Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis

J. A.C.M. Goos; V. M.H. Coupe; B. Diosdado; P. M. Delis-Van Diemen; C. Karga; J. A.M. Beliën; B. Carvalho; M. P. Van Den Tol; H. M.W. Verheul; A. A. Geldof; G. A. Meijer; O. S. Hoekstra; R. J.A. Fijneman; N. C.T. Van Grieken; L. R. Perk; E. A. Te Velde; A. D. Windhorst; J. Baas; A. M. Rijken; M. W. Van Beek; H. J. Pijpers; H. Bril; H. B.A.C. Stockmann; A. Zwijnenburg; K. Bosscha; A. J. Van Den Brule; C. J. Hoekstra; J. C. Van Der Linden; I. H. Borel Rinkes; P. J. Van Diest; R. Van Hillegersberg; O. Kranenburg; M. G. Lam; N. Snoeren; I. H. Liem; R. M. Roumen; W. Vening

doi:10.1038/bjc.2013.608

Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis

J. A.C.M. Goos, V. M.H. Coupe, B. Diosdado, P. M. Delis-Van Diemen, C. Karga, J. A.M. Beliën, B. Carvalho, M. P. Van Den Tol, H. M.W. Verheul, A. A. Geldof, G. A. Meijer, O. S. Hoekstra, R. J.A. Fijneman, N. C.T. Van Grieken, L. R. Perk, E. A. Te Velde, A. D. Windhorst, J. Baas, A. M. Rijken, M. W. Van BeekH. J. Pijpers, H. Bril, H. B.A.C. Stockmann, A. Zwijnenburg, K. Bosscha, A. J. Van Den Brule, C. J. Hoekstra, J. C. Van Der Linden, I. H. Borel Rinkes, P. J. Van Diest, R. Van Hillegersberg, O. Kranenburg, M. G. Lam, N. Snoeren, I. H. Liem, R. M. Roumen, W. Vening

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Abstract

Background:Five-year survival after resection of colorectal cancer liver metastasis (CRLCM) is <30%. We recently found that aurora kinase A (AURKA) drives 20q gain-associated tumour progression and is associated with disease recurrence. This study evaluates the prognostic value of AURKA expression in CRCLM of patients who underwent liver resection.Methods:Tissue microarrays (TMAs) were generated using formalin-fixed paraffin-embedded CRCLM and matched primary tumour from a multi-institutional cohort of patients with CRCLM who underwent liver resection between 1990 and 2010. Tissue microarrays were stained for AURKA using immunohistochemistry, and a hazard rate ratio (HRR) for the association between overall survival (OS) and nuclear AURKA expression in CRCLM was calculated. Results were validated by 500-fold cross-validation.Results:The expression of AURKA was evaluated in CRCLM of 343 patients. High AURKA expression was associated with poor OS (HRR 1.55, P<0.01), with a cross-validated average HRR of 1.57 (P=0.02). Average HRR was adjusted for the established prognostic clinicopathological variables in a multivariate analysis (average HRR 1.66; P=0.02). The expression of AURKA in CRCLM was correlated to its expression in corresponding primary tumour (P<0.01).Conclusion:The expression of AURKA protein is a molecular biomarker with prognostic value for patients with CRCLM, independent of established clinicopathological variables.

Original language	English (US)
Pages (from-to)	2445-2452
Number of pages	8
Journal	British journal of cancer
Volume	109
Issue number	9
DOIs	https://doi.org/10.1038/bjc.2013.608
State	Published - Oct 29 2013
Externally published	Yes

Keywords

AURKA
biomarker
colorectal cancer
liver metastasis
prognosis

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1038/bjc.2013.608

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Goos, J. A. C. M., Coupe, V. M. H., Diosdado, B., Delis-Van Diemen, P. M., Karga, C., Beliën, J. A. M., Carvalho, B., Van Den Tol, M. P., Verheul, H. M. W., Geldof, A. A., Meijer, G. A., Hoekstra, O. S., Fijneman, R. J. A., Van Grieken, N. C. T., Perk, L. R., Te Velde, E. A., Windhorst, A. D., Baas, J., Rijken, A. M., ... Vening, W. (2013). Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis. British journal of cancer, 109(9), 2445-2452. https://doi.org/10.1038/bjc.2013.608

Goos, JACM, Coupe, VMH, Diosdado, B, Delis-Van Diemen, PM, Karga, C, Beliën, JAM, Carvalho, B, Van Den Tol, MP, Verheul, HMW, Geldof, AA, Meijer, GA, Hoekstra, OS, Fijneman, RJA, Van Grieken, NCT, Perk, LR, Te Velde, EA, Windhorst, AD, Baas, J, Rijken, AM, Van Beek, MW, Pijpers, HJ, Bril, H, Stockmann, HBAC, Zwijnenburg, A, Bosscha, K, Van Den Brule, AJ, Hoekstra, CJ, Van Der Linden, JC, Borel Rinkes, IH, Van Diest, PJ, Van Hillegersberg, R, Kranenburg, O, Lam, MG, Snoeren, N, Liem, IH, Roumen, RM & Vening, W 2013, 'Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis', British journal of cancer, vol. 109, no. 9, pp. 2445-2452. https://doi.org/10.1038/bjc.2013.608

@article{d00d2aec809243058f7e9d4e46d9c9a6,

title = "Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis",

abstract = "Background:Five-year survival after resection of colorectal cancer liver metastasis (CRLCM) is <30%. We recently found that aurora kinase A (AURKA) drives 20q gain-associated tumour progression and is associated with disease recurrence. This study evaluates the prognostic value of AURKA expression in CRCLM of patients who underwent liver resection.Methods:Tissue microarrays (TMAs) were generated using formalin-fixed paraffin-embedded CRCLM and matched primary tumour from a multi-institutional cohort of patients with CRCLM who underwent liver resection between 1990 and 2010. Tissue microarrays were stained for AURKA using immunohistochemistry, and a hazard rate ratio (HRR) for the association between overall survival (OS) and nuclear AURKA expression in CRCLM was calculated. Results were validated by 500-fold cross-validation.Results:The expression of AURKA was evaluated in CRCLM of 343 patients. High AURKA expression was associated with poor OS (HRR 1.55, P<0.01), with a cross-validated average HRR of 1.57 (P=0.02). Average HRR was adjusted for the established prognostic clinicopathological variables in a multivariate analysis (average HRR 1.66; P=0.02). The expression of AURKA in CRCLM was correlated to its expression in corresponding primary tumour (P<0.01).Conclusion:The expression of AURKA protein is a molecular biomarker with prognostic value for patients with CRCLM, independent of established clinicopathological variables.",

keywords = "AURKA, biomarker, colorectal cancer, liver metastasis, prognosis",

author = "Goos, {J. A.C.M.} and Coupe, {V. M.H.} and B. Diosdado and {Delis-Van Diemen}, {P. M.} and C. Karga and Beli{\"e}n, {J. A.M.} and B. Carvalho and {Van Den Tol}, {M. P.} and Verheul, {H. M.W.} and Geldof, {A. A.} and Meijer, {G. A.} and Hoekstra, {O. S.} and Fijneman, {R. J.A.} and {Van Grieken}, {N. C.T.} and Perk, {L. R.} and {Te Velde}, {E. A.} and Windhorst, {A. D.} and J. Baas and Rijken, {A. M.} and {Van Beek}, {M. W.} and Pijpers, {H. J.} and H. Bril and Stockmann, {H. B.A.C.} and A. Zwijnenburg and K. Bosscha and {Van Den Brule}, {A. J.} and Hoekstra, {C. J.} and {Van Der Linden}, {J. C.} and {Borel Rinkes}, {I. H.} and {Van Diest}, {P. J.} and {Van Hillegersberg}, R. and O. Kranenburg and Lam, {M. G.} and N. Snoeren and Liem, {I. H.} and Roumen, {R. M.} and W. Vening",

note = "Funding Information: Funding was supported by the Center for Translational Molecular Medicine, DeCoDe project (grant 03O-101).",

year = "2013",

month = oct,

day = "29",

doi = "10.1038/bjc.2013.608",

language = "English (US)",

volume = "109",

pages = "2445--2452",

journal = "British journal of cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "9",

}

TY - JOUR

T1 - Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis

AU - Goos, J. A.C.M.

AU - Coupe, V. M.H.

AU - Diosdado, B.

AU - Delis-Van Diemen, P. M.

AU - Karga, C.

AU - Beliën, J. A.M.

AU - Carvalho, B.

AU - Van Den Tol, M. P.

AU - Verheul, H. M.W.

AU - Geldof, A. A.

AU - Meijer, G. A.

AU - Hoekstra, O. S.

AU - Fijneman, R. J.A.

AU - Van Grieken, N. C.T.

AU - Perk, L. R.

AU - Te Velde, E. A.

AU - Windhorst, A. D.

AU - Baas, J.

AU - Rijken, A. M.

AU - Van Beek, M. W.

AU - Pijpers, H. J.

AU - Bril, H.

AU - Stockmann, H. B.A.C.

AU - Zwijnenburg, A.

AU - Bosscha, K.

AU - Van Den Brule, A. J.

AU - Hoekstra, C. J.

AU - Van Der Linden, J. C.

AU - Borel Rinkes, I. H.

AU - Van Diest, P. J.

AU - Van Hillegersberg, R.

AU - Kranenburg, O.

AU - Lam, M. G.

AU - Snoeren, N.

AU - Liem, I. H.

AU - Roumen, R. M.

AU - Vening, W.

N1 - Funding Information: Funding was supported by the Center for Translational Molecular Medicine, DeCoDe project (grant 03O-101).

PY - 2013/10/29

Y1 - 2013/10/29

N2 - Background:Five-year survival after resection of colorectal cancer liver metastasis (CRLCM) is <30%. We recently found that aurora kinase A (AURKA) drives 20q gain-associated tumour progression and is associated with disease recurrence. This study evaluates the prognostic value of AURKA expression in CRCLM of patients who underwent liver resection.Methods:Tissue microarrays (TMAs) were generated using formalin-fixed paraffin-embedded CRCLM and matched primary tumour from a multi-institutional cohort of patients with CRCLM who underwent liver resection between 1990 and 2010. Tissue microarrays were stained for AURKA using immunohistochemistry, and a hazard rate ratio (HRR) for the association between overall survival (OS) and nuclear AURKA expression in CRCLM was calculated. Results were validated by 500-fold cross-validation.Results:The expression of AURKA was evaluated in CRCLM of 343 patients. High AURKA expression was associated with poor OS (HRR 1.55, P<0.01), with a cross-validated average HRR of 1.57 (P=0.02). Average HRR was adjusted for the established prognostic clinicopathological variables in a multivariate analysis (average HRR 1.66; P=0.02). The expression of AURKA in CRCLM was correlated to its expression in corresponding primary tumour (P<0.01).Conclusion:The expression of AURKA protein is a molecular biomarker with prognostic value for patients with CRCLM, independent of established clinicopathological variables.

AB - Background:Five-year survival after resection of colorectal cancer liver metastasis (CRLCM) is <30%. We recently found that aurora kinase A (AURKA) drives 20q gain-associated tumour progression and is associated with disease recurrence. This study evaluates the prognostic value of AURKA expression in CRCLM of patients who underwent liver resection.Methods:Tissue microarrays (TMAs) were generated using formalin-fixed paraffin-embedded CRCLM and matched primary tumour from a multi-institutional cohort of patients with CRCLM who underwent liver resection between 1990 and 2010. Tissue microarrays were stained for AURKA using immunohistochemistry, and a hazard rate ratio (HRR) for the association between overall survival (OS) and nuclear AURKA expression in CRCLM was calculated. Results were validated by 500-fold cross-validation.Results:The expression of AURKA was evaluated in CRCLM of 343 patients. High AURKA expression was associated with poor OS (HRR 1.55, P<0.01), with a cross-validated average HRR of 1.57 (P=0.02). Average HRR was adjusted for the established prognostic clinicopathological variables in a multivariate analysis (average HRR 1.66; P=0.02). The expression of AURKA in CRCLM was correlated to its expression in corresponding primary tumour (P<0.01).Conclusion:The expression of AURKA protein is a molecular biomarker with prognostic value for patients with CRCLM, independent of established clinicopathological variables.

KW - AURKA

KW - biomarker

KW - colorectal cancer

KW - liver metastasis

KW - prognosis

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U2 - 10.1038/bjc.2013.608

DO - 10.1038/bjc.2013.608

M3 - Article

C2 - 24104968

AN - SCOPUS:84887024229

SN - 0007-0920

VL - 109

SP - 2445

EP - 2452

JO - British journal of cancer

JF - British journal of cancer

IS - 9

ER -

Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis

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Keywords

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