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.

• Authors: 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
• Journal: JAMA internal medicine (JAMA Intern Med) Vol. 174 Issue 5 Pg. 732-9 (May 2014) ISSN: 2168-6114 [Electronic] United States
• PMID: 24687028 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Histocompatibility Antigens Class I
• Cyclooxygenase 2
• Phosphatidylinositol 3-Kinases
• Class I Phosphatidylinositol 3-Kinases
• PIK3CA protein, human
• Aspirin

Topics

• Aspirin (therapeutic use)
• Biomarkers, Tumor (analysis, genetics)
• Class I Phosphatidylinositol 3-Kinases
• Cohort Studies
• Colonic Neoplasms (drug therapy, genetics, mortality)
• Cyclooxygenase 2 (analysis, genetics)
• DNA Mutational Analysis
• Female
• Gene Expression
• Histocompatibility Antigens Class I (analysis)
• Humans
• Immunohistochemistry
• Male
• Mutation
• Phosphatidylinositol 3-Kinases (analysis)
• Polymerase Chain Reaction
• Registries
• Tissue Array Analysis