Gene expression and effects of orally active derivatives of fluoropyrimidine on gastric and colorectal cancer

The effects of chemotherapy on gastrointestinal cancer are influenced by the chemotherapeutic sensitivity of the cancer cells. Determining the expression of genes related to chemotherapeutic sensitivity has been used as a molecular method. The aim of the study was to clarify the relationships between the expression of genes related to chemotherapeutic sensitivity and the effects of orally active derivatives of fluoropyrimidine on gastric and colorectal cancer. Forty-five patients who underwent adjuvant chemotherapy containing orally active derivatives of fluoropyrimidine after undergoing curative surgery for gastric or colorectal cancer were enrolled. Twenty-four patients had colorectal cancer and 21 patients had gastric cancer. Total RNA was extracted from formal in-fixed, paraffin-embedded specimens of the resected tumors, and the expression of 11 genes was measured using the RT-PCR method. We then analyzed the relationships between the gene expression and the postoperative relapse rate as well as the relationships between clinicopathological factors and postoperative relapse rate. The median observation period of the subjects was 41 months. Twelve out of the 21 gastric cancer patients (57%) and 11 out of the 24 colorectal cancer patients (46%) relapsed. Although the :results of a univariate analysis revealed that expression of none of the evaluated genes was related to relapse in the gastric cancer patients, excision repair cross-complementing gene 1 (ERCC1) overexpression was related to the relapse rate in colorectal cancer patients (p=0.023). When 1.295 was set as the cut-off value for ERCC1 overexpression using the receiver operating characteristic (ROC) curve, 67% of patients with ERCC1 overexpression and 25% of patients without ERCC1 overexpression relapsed. The relapse-free survival rate was lower in the group with ERCC1 overexpression than in the group without ERCC1 overexpression (p=0.046). ERCC1 overexpression appears to be a useful predictor of relapse in colorectal cancer patients receiving adjuvant therapy with regimens including orally active derivatives of fluoropyrimidine.