Research shows how aspirin may act on blood platelets to improve survival in colon cancer patients

Researchers believe they have discovered how aspirin improves survival in patients diagnosed with colon cancer, the 2013 European Cancer Congress (ECC2013) [1] heard today (Monday).

Although previous research has shown that taking low dose aspirin after being diagnosed with colon cancer improves patient outcome, the reasons why this happens remain unknown. The new research has shown that aspirin improves outcome in patients whose tumour cells express a specific protein on their surface; the protein is known as Human Leukocyte Antigen class I (HLA class I), a cell-surface protein produced by a collection of genes involved in the functioning of the immune system.

The results mean that HLA class I could be used in the future to predict whether or not a patient would benefit from aspirin. The findings also suggest that aspirin's role in improved patient survival could be explained by the interaction of the body's immune system with the effect of aspirin on platelets (cell fragments in the blood that are involved in clotting).

Dr Marlies Reimers, MD, a PhD student, in the Department of Surgery, Leiden University Medical Center, The Netherlands, said: We think that platelets are involved in cancer spreading to other parts of the body by shielding tumour cells in the bloodstream so that they cannot be recognised by the immune system and can finally colonise distant organs. Aspirin could help to 'unmask' those tumour cells by attacking platelet formation, so that the immune cells can detect and eliminate them.

Dr Reimers and her colleagues used tissue microarray technology [2] to investigate the pattern of protein expression in colon cancer patients whose aspirin use after cancer diagnosis was known and who were registered with the Eindhoven Cancer Registry between 1998 and 2007. They studied 999 colon cancers to look at HLA class I expression, and expression of the COX-2 enzyme. They also extracted DNA from 663 tumours to look for mutations in the PIK3CA gene. Both COX-2 expression and PIK3CA mutations are known to be involved in the onset of cancer.

They found that low dose (80mg a day) aspirin use after diagnosis improved survival only in patients with tumours expressing HLA class I; if these patients used aspirin they were half as likely to die during the average four years of follow-up as patients with tumours expressing HLA class I that did not use aspirin. This effect of aspirin was not seen in patients without HLA class I expression. Therefore, HLA class I might serve as a predictive biomarker to help identify patients who would benefit from aspirin therapy after diagnosis, said Dr Reimers.

Our results showed that there was no difference in the effect of aspirin in relation to COX-2 expression and PIK3CA mutation.

Until now it was assumed that COX-2 expression or PIK3CA gene mutation played a role in the effectiveness of aspirin use. Dr Reimers explained: When we stratified our analyses for COX-2 expression and PIK3CA mutation status, we did not see differences in survival benefit. For example, patients with aspirin use after diagnosis with strong COX-2 expressing tumours had the same survival benefit as tumours with weak COX-2 expression.