Expression of HLA class I antigen, aspirin use, and survival after a diagnosis of colon cancer

Marlies S Reimers; Esther Bastiaannet; Ruth E Langley; Ronald van Eijk; Ronald L P van Vlierberghe; Valery E P Lemmens; Myrthe P P van Herk-Sukel; Tom van Wezel; Riccardo Fodde; Peter J K Kuppen; Hans Morreau; Cornelis J H van de Velde; Gerrit Jan Liefers

doi:10.1001/jamainternmed.2014.511

Expression of HLA class I antigen, aspirin use, and survival after a diagnosis of colon cancer

Marlies S Reimers
, Esther Bastiaannet
, Ruth E Langley
, Ronald van Eijk
, Ronald L P van Vlierberghe
, Valery E P Lemmens
, Myrthe P P van Herk-Sukel
, Tom van Wezel
, Riccardo Fodde
, Peter J K Kuppen
, Hans Morreau
, Cornelis J H van de Velde
, Gerrit Jan Liefers

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

Abstract

IMPORTANCE: Use of aspirin (which inhibits platelet function) after a colon cancer diagnosis is associated with improved overall survival. Identifying predictive biomarkers of this effect could individualize therapy and decrease toxic effects.

OBJECTIVE: To demonstrate that survival benefit associated with low-dose aspirin use after a diagnosis of colorectal cancer might depend on HLA class I antigen expression.

DESIGN, SETTING, AND PARTICIPANTS: A cohort study with tumor blocks from 999 patients with colon cancer (surgically resected between 2002 and 2008), analyzed for HLA class I antigen and prostaglandin endoperoxide synthase 2 (PTGS2) expression using a tissue microarray. Mutation analysis of PIK3CA was also performed. Data on aspirin use after diagnosis were obtained from a prescription database. Parametric survival models with exponential (Poisson) distribution were used to model the survival.

MAIN OUTCOMES AND MEASURES: Overall survival.

RESULTS: The overall survival benefit associated with aspirin use after a diagnosis of colon cancer had an adjusted rate ratio (RR) of 0.53 (95% CI, 0.38-0.74; P < .001) when tumors expressed HLA class I antigen compared with an RR of 1.03 (0.66-1.61; P = .91) when HLA antigen expression was lost. The benefit of aspirin was similar for tumors with strong PTGS2 expression (0.68; 0.48-0.97; P = .03), weak PTGS2 expression (0.59; 0.38-0.97; P = .02), and wild-type PIK3CA tumors (0.55; 0.40-0.75; P < .001). No association was observed with mutated PIK3CA tumors (0.73; 0.33-1.63; P = .44).

CONCLUSIONS AND RELEVANCE: Contrary to the original hypothesis, aspirin use after colon cancer diagnosis was associated with improved survival if tumors expressed HLA class I antigen. Increased PTGS2 expression or the presence of mutated PIK3CA did not predict benefit from aspirin. HLA class I antigen might serve as a predictive biomarker for adjuvant aspirin therapy in colon cancer.

Original language	English
Pages (from-to)	732-9
Number of pages	8
Journal	JAMA Internal Medicine
Volume	174
Issue number	5
DOIs	https://doi.org/10.1001/jamainternmed.2014.511
Publication status	Published - 2014
Externally published	Yes

Keywords

Aspirin
Biomarkers, Tumor
Cohort Studies
Colonic Neoplasms
Cyclooxygenase 2
DNA Mutational Analysis
Female
Gene Expression
Histocompatibility Antigens Class I
Humans
Immunohistochemistry
Male
Mutation
Phosphatidylinositol 3-Kinases
Polymerase Chain Reaction
Registries
Tissue Array Analysis
Journal Article

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10.1001/jamainternmed.2014.511

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Reimers, M. S., Bastiaannet, E., Langley, R. E., van Eijk, R., van Vlierberghe, R. L. P., Lemmens, V. E. P., van Herk-Sukel, M. P. P., van Wezel, T., Fodde, R., Kuppen, P. J. K., Morreau, H., van de Velde, C. J. H., & Liefers, G. J. (2014). Expression of HLA class I antigen, aspirin use, and survival after a diagnosis of colon cancer. JAMA Internal Medicine, 174(5), 732-9. https://doi.org/10.1001/jamainternmed.2014.511

@article{ea63d854aace4a819ff820c415b858a3,

title = "Expression of HLA class I antigen, aspirin use, and survival after a diagnosis of colon cancer",

abstract = "IMPORTANCE: Use of aspirin (which inhibits platelet function) after a colon cancer diagnosis is associated with improved overall survival. Identifying predictive biomarkers of this effect could individualize therapy and decrease toxic effects.OBJECTIVE: To demonstrate that survival benefit associated with low-dose aspirin use after a diagnosis of colorectal cancer might depend on HLA class I antigen expression.DESIGN, SETTING, AND PARTICIPANTS: A cohort study with tumor blocks from 999 patients with colon cancer (surgically resected between 2002 and 2008), analyzed for HLA class I antigen and prostaglandin endoperoxide synthase 2 (PTGS2) expression using a tissue microarray. Mutation analysis of PIK3CA was also performed. Data on aspirin use after diagnosis were obtained from a prescription database. Parametric survival models with exponential (Poisson) distribution were used to model the survival.MAIN OUTCOMES AND MEASURES: Overall survival.RESULTS: The overall survival benefit associated with aspirin use after a diagnosis of colon cancer had an adjusted rate ratio (RR) of 0.53 (95\% CI, 0.38-0.74; P < .001) when tumors expressed HLA class I antigen compared with an RR of 1.03 (0.66-1.61; P = .91) when HLA antigen expression was lost. The benefit of aspirin was similar for tumors with strong PTGS2 expression (0.68; 0.48-0.97; P = .03), weak PTGS2 expression (0.59; 0.38-0.97; P = .02), and wild-type PIK3CA tumors (0.55; 0.40-0.75; P < .001). No association was observed with mutated PIK3CA tumors (0.73; 0.33-1.63; P = .44).CONCLUSIONS AND RELEVANCE: Contrary to the original hypothesis, aspirin use after colon cancer diagnosis was associated with improved survival if tumors expressed HLA class I antigen. Increased PTGS2 expression or the presence of mutated PIK3CA did not predict benefit from aspirin. HLA class I antigen might serve as a predictive biomarker for adjuvant aspirin therapy in colon cancer.",

keywords = "Aspirin, Biomarkers, Tumor, Cohort Studies, Colonic Neoplasms, Cyclooxygenase 2, DNA Mutational Analysis, Female, Gene Expression, Histocompatibility Antigens Class I, Humans, Immunohistochemistry, Male, Mutation, Phosphatidylinositol 3-Kinases, Polymerase Chain Reaction, Registries, Tissue Array Analysis, Journal Article",

author = "Reimers, \{Marlies S\} and Esther Bastiaannet and Langley, \{Ruth E\} and \{van Eijk\}, Ronald and \{van Vlierberghe\}, \{Ronald L P\} and Lemmens, \{Valery E P\} and \{van Herk-Sukel\}, \{Myrthe P P\} and \{van Wezel\}, Tom and Riccardo Fodde and Kuppen, \{Peter J K\} and Hans Morreau and \{van de Velde\}, \{Cornelis J H\} and Liefers, \{Gerrit Jan\}",

year = "2014",

doi = "10.1001/jamainternmed.2014.511",

language = "English",

volume = "174",

pages = "732--9",

journal = "JAMA Internal Medicine",

issn = "2168-6106",

publisher = "American Medical Association",

number = "5",

}

Reimers, MS, Bastiaannet, E, Langley, RE, van Eijk, R, van Vlierberghe, RLP, Lemmens, VEP, van Herk-Sukel, MPP, van Wezel, T, Fodde, R, Kuppen, PJK, Morreau, H, van de Velde, CJH & Liefers, GJ 2014, 'Expression of HLA class I antigen, aspirin use, and survival after a diagnosis of colon cancer', JAMA Internal Medicine, vol. 174, no. 5, pp. 732-9. https://doi.org/10.1001/jamainternmed.2014.511

TY - JOUR

T1 - Expression of HLA class I antigen, aspirin use, and survival after a diagnosis of colon cancer

AU - Reimers, Marlies S

AU - Bastiaannet, Esther

AU - Langley, Ruth E

AU - van Eijk, Ronald

AU - van Vlierberghe, Ronald L P

AU - Lemmens, Valery E P

AU - van Herk-Sukel, Myrthe P P

AU - van Wezel, Tom

AU - Fodde, Riccardo

AU - Kuppen, Peter J K

AU - Morreau, Hans

AU - van de Velde, Cornelis J H

AU - Liefers, Gerrit Jan

PY - 2014

Y1 - 2014

N2 - IMPORTANCE: Use of aspirin (which inhibits platelet function) after a colon cancer diagnosis is associated with improved overall survival. Identifying predictive biomarkers of this effect could individualize therapy and decrease toxic effects.OBJECTIVE: To demonstrate that survival benefit associated with low-dose aspirin use after a diagnosis of colorectal cancer might depend on HLA class I antigen expression.DESIGN, SETTING, AND PARTICIPANTS: A cohort study with tumor blocks from 999 patients with colon cancer (surgically resected between 2002 and 2008), analyzed for HLA class I antigen and prostaglandin endoperoxide synthase 2 (PTGS2) expression using a tissue microarray. Mutation analysis of PIK3CA was also performed. Data on aspirin use after diagnosis were obtained from a prescription database. Parametric survival models with exponential (Poisson) distribution were used to model the survival.MAIN OUTCOMES AND MEASURES: Overall survival.RESULTS: The overall survival benefit associated with aspirin use after a diagnosis of colon cancer had an adjusted rate ratio (RR) of 0.53 (95% CI, 0.38-0.74; P < .001) when tumors expressed HLA class I antigen compared with an RR of 1.03 (0.66-1.61; P = .91) when HLA antigen expression was lost. The benefit of aspirin was similar for tumors with strong PTGS2 expression (0.68; 0.48-0.97; P = .03), weak PTGS2 expression (0.59; 0.38-0.97; P = .02), and wild-type PIK3CA tumors (0.55; 0.40-0.75; P < .001). No association was observed with mutated PIK3CA tumors (0.73; 0.33-1.63; P = .44).CONCLUSIONS AND RELEVANCE: Contrary to the original hypothesis, aspirin use after colon cancer diagnosis was associated with improved survival if tumors expressed HLA class I antigen. Increased PTGS2 expression or the presence of mutated PIK3CA did not predict benefit from aspirin. HLA class I antigen might serve as a predictive biomarker for adjuvant aspirin therapy in colon cancer.

AB - IMPORTANCE: Use of aspirin (which inhibits platelet function) after a colon cancer diagnosis is associated with improved overall survival. Identifying predictive biomarkers of this effect could individualize therapy and decrease toxic effects.OBJECTIVE: To demonstrate that survival benefit associated with low-dose aspirin use after a diagnosis of colorectal cancer might depend on HLA class I antigen expression.DESIGN, SETTING, AND PARTICIPANTS: A cohort study with tumor blocks from 999 patients with colon cancer (surgically resected between 2002 and 2008), analyzed for HLA class I antigen and prostaglandin endoperoxide synthase 2 (PTGS2) expression using a tissue microarray. Mutation analysis of PIK3CA was also performed. Data on aspirin use after diagnosis were obtained from a prescription database. Parametric survival models with exponential (Poisson) distribution were used to model the survival.MAIN OUTCOMES AND MEASURES: Overall survival.RESULTS: The overall survival benefit associated with aspirin use after a diagnosis of colon cancer had an adjusted rate ratio (RR) of 0.53 (95% CI, 0.38-0.74; P < .001) when tumors expressed HLA class I antigen compared with an RR of 1.03 (0.66-1.61; P = .91) when HLA antigen expression was lost. The benefit of aspirin was similar for tumors with strong PTGS2 expression (0.68; 0.48-0.97; P = .03), weak PTGS2 expression (0.59; 0.38-0.97; P = .02), and wild-type PIK3CA tumors (0.55; 0.40-0.75; P < .001). No association was observed with mutated PIK3CA tumors (0.73; 0.33-1.63; P = .44).CONCLUSIONS AND RELEVANCE: Contrary to the original hypothesis, aspirin use after colon cancer diagnosis was associated with improved survival if tumors expressed HLA class I antigen. Increased PTGS2 expression or the presence of mutated PIK3CA did not predict benefit from aspirin. HLA class I antigen might serve as a predictive biomarker for adjuvant aspirin therapy in colon cancer.

KW - Aspirin

KW - Biomarkers, Tumor

KW - Cohort Studies

KW - Colonic Neoplasms

KW - Cyclooxygenase 2

KW - DNA Mutational Analysis

KW - Female

KW - Gene Expression

KW - Histocompatibility Antigens Class I

KW - Humans

KW - Immunohistochemistry

KW - Male

KW - Mutation

KW - Phosphatidylinositol 3-Kinases

KW - Polymerase Chain Reaction

KW - Registries

KW - Tissue Array Analysis

KW - Journal Article

U2 - 10.1001/jamainternmed.2014.511

DO - 10.1001/jamainternmed.2014.511

M3 - Article

C2 - 24687028

SN - 2168-6106

VL - 174

SP - 732

EP - 739

JO - JAMA Internal Medicine

JF - JAMA Internal Medicine

IS - 5

ER -

Expression of HLA class I antigen, aspirin use, and survival after a diagnosis of colon cancer

Abstract

Keywords

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