How aspirin improves survival in colon cancer
Aspirin improves outcomes in patients whose tumor cells express a specific protein on their surface that is known as human leukocyte antigen class I (HLA class I), according to research presented at the 2013 European Cancer Congress in Amsterdam, The Netherlands.
HLA class I is a cell-surface protein produced by a collection of genes involved in the functioning of the immune system. Though low-dose aspirin has been known to improve patient outcomes in colon cancer, this study will allow HLA class I status to be used to predict if a patient would benefit from aspirin. These 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.
"We think that platelets are involved in cancer spreading to other parts of the body by shielding tumor cells in the bloodstream so that they cannot be recognized by the immune system and can finally colonize distant organs. Aspirin could help to unmask those tumor cells by attacking platelet formation, so that the immune cells can detect and eliminate them," explained PhD student Marlies Reimers, MD, of Leiden University Medical Center in The Netherlands.
Reimers and her colleagues used tissue microarray technology to investigate the protein expression patterns of 999 patients with colon cancer whose aspirin use after cancer diagnosis was known. The expression of HLA class I and of the COX-2 enzyme was investigated. Also, DNA was extracted to analyze PIK3CA mutations. Both COX-2 expression and PIK3CA mutations are known to be involved in the onset of cancer.
Low-dose (80 mg/day) aspirin use after diagnosis improved survival only in patients with tumors expressing HLA class I. These patients were half as likely to die during the average 4 years of follow-up as patients whose tumors expressed HLA class I but who did not use aspirin.
Until now it was assumed that COX-2 expression or PIK3CA gene mutation played a role in the effectiveness of aspirin use. 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 tumors had the same survival benefit as tumors with weak COX-2 expression."
Reimers and her colleagues believe their results suggest that aspirin may be acting on two different pathways in colon cancer: one in the preventive setting and the other through the control of metastasis.