Evaluation of TS and ENOSF1 Variants as a Biomarker in Response to Neoadjuvant Chemotherapy based on 5FU in Gastric Cancer Patients

OBJECTIVE: Neoadjuvant chemotherapy with 5-fluorouracil (5FU) is one of the most effective treatment options for gastric cancer patients. However, treatment response varies significantly between patients based on their genetic profile. The purpose of this study was to determine the association between thymidylate synthase (TS) and enolase superfamily member 1 (ENOSF1) polymorphisms, treatment response, and overall survival in patients with gastric cancer. METHODS: The TS and ENOSF1 variants were analyzed in formalin-fixed paraffin-embedded (FFPE) tissue from 100 gastric cancer patients receiving neoadjuvant 5FU-based chemotherapy. Polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) were used to determine TS polymorphisms’ genotypes, and the Tetra Arms PCR method was used to identify ENOSF1 polymorphisms. Patients were followed for up to five years, and the association between variants, treatment response, and overall survival (OS) was examined. RESULTS: There was a significant association between the TS 5’ UTR polymorphism and response to treatment in patients with gastric cancer who received neoadjuvant 5FU therapy (P=0.032). Patients with the 2R3R genotype responded better to treatment, whereas those with the 3R3R genotype did not respond to treatment. Patients with the 2R2R and 3R3R genotypes had the longest and shortest median survival times, respectively, and the observed differences were significant (p=0.003). There was a statistically significant relationship between rs2612091 and chemotherapy response (P=0.017). Patients with genotype AG did not respond to treatment. CONCLUSION: This study established that the TS 5’ UTR and ENOSF1 rs2612091 polymorphisms could be used to predict treatment response and overall survival in patients with gastric cancer who received neoadjuvant chemotherapy based on 5FU.