RESUMO
OBJECTIVES: The correlations of the ratio of long-/short-chain DNA fragments in blood with the existence of cancer and the clinicopathological features of colorectal cancer (CRC) were examined. The potential use of this ratio for diagnostic screening was evaluated. METHODS: DNA concentrations were amplified using Alu247 for long-chain DNA fragments and Alu115 for long- and short-chain DNA fragments. The Alu247/115 ratio was calculated for 60 patients with CRC and 24 healthy volunteers. The correlation of the Alu247/115 ratio with clinicopathological variables and the efficacy of this ratio as a tumor marker were examined. The Alu247/115 ratio cut-off value was set using a receiver operating characteristic (ROC) curve. RESULTS: The Alu247/115 ratio was significantly higher in patients with CRC than in healthy volunteers (P<0.001). The Alu247/115 ratio was also significantly higher in patients with Dukes stage A or B CRC than in healthy volunteers (P=0.034) as well as in patients with Dukes C or D CRC than in those with Dukes A or B CRC (P=0.016). Among patients with CRC, the Alu247/115 ratio was significantly higher in those with than without venous invasion (P=0.031). Using the cut-off value set from the ROC curve, the sensitivity of the Alu247/115 ratio was significantly higher than that of the carcinoembryonic antigen level (P=0.004) or the carbohydrate antigen 19-9 level (P<0.001). CONCLUSION: Our data suggest that the Alu247/115 ratio is a promising tool for highly sensitive and early detection of CRC.
RESUMO
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 formalin-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.
