Investigation of gene expression of the candidate tumor markers that can be used for follow up the effectiveness of rectal cancer treatment

Objective: The disease recurrence or resistance to neoadjuvant treatment develops due to the adaptation to hypoxia, apoptosis or autophagy. Survivin as being one of the inhibitor of apoptosis, Beclin 1 which is a positive regulator in the autophagy pathway, and hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase 9 (CA9) which are associated with tumor tissue hypoxia and their gene product may be related with resistance to treatment by apoptosis, autophagy and hypoxic pathways that they affect. Thus, we aimed to illuminate the effects on treatment resistance by following changes in the gene expressions of these potential tumor markers that may help to monitor the response to neoadjuvant treatment in locally advanced rectal cancer (RC). Method: Twenty-five patients with locally advanced RC received neoadjuvant therapy were included in the study. Gene expression and protein levels of Beclin 1, survivin, HIF-1α and CA9 were analyzed in fresh tissue and blood samples. The relationship of these markers with tumor staging and regression grade of patients were evaluated. Results: Higher blood CA9 gene expression levels and lower blood HIF-1α protein levels were found in the group responded to neoadjuvant treatment according to tumor regression grade. After neoadjuvant treatment in patients, tissue Beclin 1 and blood survivin gene expressions, and tissue CA9, blood Beclin 1 and blood HIF-1α protein levels decreased significantly. Conclusion: Beclin 1, survivin, hypoxia-inducible factor-1 alpha and carbonic anhydrase-9 were considered as potential markers that might provide benefit in the prediction of the effects of the applied neoadjuvant treatment approach.