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Thymidine phosphorylase mRNA expression may be a predictor of response to post-operative adjuvant chemotherapy with S-1 in patients with stage III colorectal cancer.

Ogawa M, Watanabe M, Mitsuyama Y, Anan T, Ohkuma M, Kobayashi T, Eto K, Yanaga K - Oncol Lett (2014)

Bottom Line: DFS was not significantly associated with the relative mRNA expression level of any metabolizing enzyme in the study group as a whole, but there was a trend toward longer DFS in patients with high TP expression (P=0.066).In patients with stage III colorectal cancer, high TP expression was associated with significantly improved outcomes compared with low TP expression (P=0.039).These results indicate that the mRNA expression of TP, a metabolizing enzyme of 5-FU, is a significant predictor of response to post-operative chemotherapy with S-1 in patients with stage III colorectal cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo 105-8461, Japan.

ABSTRACT
The aim of the present study was to investigate markers in surgically resected specimens of colorectal cancer that can be used to predict the response to chemotherapy. The mRNA expression levels of enzymes involved in 5-fluorouracil (5-FU) metabolism and folate metabolism were measured in formalin-fixed, paraffin-embedded tumor sections obtained from the primary tumors of 54 patients with resected stage II or III colorectal cancer who received S-1 for one year. The 5-FU metabolizing enzymes studied were thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase (TP). The folate metabolizing enzymes studied were folypolyglutamate synthetase, γ-glutamyl hydrolase and dihydrofolate reductase. The associations between the mRNA expression levels of these enzymes and clinical variables were investigated. Tumors were classified as exhibiting high or low expression as compared with the median mRNA expression level of each metabolizing enzyme defined as the cutoff value. The associations between the high and low expression levels of each enzyme and disease-free survival (DFS) were analyzed with the use of Kaplan-Meier curves and the log-rank test. DFS was not significantly associated with the relative mRNA expression level of any metabolizing enzyme in the study group as a whole, but there was a trend toward longer DFS in patients with high TP expression (P=0.066). In patients with stage III colorectal cancer, high TP expression was associated with significantly improved outcomes compared with low TP expression (P=0.039). These results indicate that the mRNA expression of TP, a metabolizing enzyme of 5-FU, is a significant predictor of response to post-operative chemotherapy with S-1 in patients with stage III colorectal cancer.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier plot of disease-free survival for stage III colorectal cancer patients according to thymidine phosphorylase (TP) expression level.
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f1-ol-08-06-2463: Kaplan-Meier plot of disease-free survival for stage III colorectal cancer patients according to thymidine phosphorylase (TP) expression level.

Mentions: DFS did not differ significantly between the patients with high mRNA expression and those with low mRNA expression of any factor associated with the sensitivity to various types of anticancer agents in the study group as a whole, but there was a trend toward a longer DFS in the patients with high TP expression (P=0.066). According to disease stage, no factor was associated with survival in the patients with stage II disease. However, in the patients with stage III disease who received post-operative adjuvant chemotherapy, there was a statistical difference between the association of low TP expression levels and DFS compared with high TP expression levels (P=0.039) (Fig. 1). DFS did not differ significantly according to the expression level of any other factor (Table IV).


Thymidine phosphorylase mRNA expression may be a predictor of response to post-operative adjuvant chemotherapy with S-1 in patients with stage III colorectal cancer.

Ogawa M, Watanabe M, Mitsuyama Y, Anan T, Ohkuma M, Kobayashi T, Eto K, Yanaga K - Oncol Lett (2014)

Kaplan-Meier plot of disease-free survival for stage III colorectal cancer patients according to thymidine phosphorylase (TP) expression level.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214505&req=5

f1-ol-08-06-2463: Kaplan-Meier plot of disease-free survival for stage III colorectal cancer patients according to thymidine phosphorylase (TP) expression level.
Mentions: DFS did not differ significantly between the patients with high mRNA expression and those with low mRNA expression of any factor associated with the sensitivity to various types of anticancer agents in the study group as a whole, but there was a trend toward a longer DFS in the patients with high TP expression (P=0.066). According to disease stage, no factor was associated with survival in the patients with stage II disease. However, in the patients with stage III disease who received post-operative adjuvant chemotherapy, there was a statistical difference between the association of low TP expression levels and DFS compared with high TP expression levels (P=0.039) (Fig. 1). DFS did not differ significantly according to the expression level of any other factor (Table IV).

Bottom Line: DFS was not significantly associated with the relative mRNA expression level of any metabolizing enzyme in the study group as a whole, but there was a trend toward longer DFS in patients with high TP expression (P=0.066).In patients with stage III colorectal cancer, high TP expression was associated with significantly improved outcomes compared with low TP expression (P=0.039).These results indicate that the mRNA expression of TP, a metabolizing enzyme of 5-FU, is a significant predictor of response to post-operative chemotherapy with S-1 in patients with stage III colorectal cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo 105-8461, Japan.

ABSTRACT
The aim of the present study was to investigate markers in surgically resected specimens of colorectal cancer that can be used to predict the response to chemotherapy. The mRNA expression levels of enzymes involved in 5-fluorouracil (5-FU) metabolism and folate metabolism were measured in formalin-fixed, paraffin-embedded tumor sections obtained from the primary tumors of 54 patients with resected stage II or III colorectal cancer who received S-1 for one year. The 5-FU metabolizing enzymes studied were thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase (TP). The folate metabolizing enzymes studied were folypolyglutamate synthetase, γ-glutamyl hydrolase and dihydrofolate reductase. The associations between the mRNA expression levels of these enzymes and clinical variables were investigated. Tumors were classified as exhibiting high or low expression as compared with the median mRNA expression level of each metabolizing enzyme defined as the cutoff value. The associations between the high and low expression levels of each enzyme and disease-free survival (DFS) were analyzed with the use of Kaplan-Meier curves and the log-rank test. DFS was not significantly associated with the relative mRNA expression level of any metabolizing enzyme in the study group as a whole, but there was a trend toward longer DFS in patients with high TP expression (P=0.066). In patients with stage III colorectal cancer, high TP expression was associated with significantly improved outcomes compared with low TP expression (P=0.039). These results indicate that the mRNA expression of TP, a metabolizing enzyme of 5-FU, is a significant predictor of response to post-operative chemotherapy with S-1 in patients with stage III colorectal cancer.

No MeSH data available.


Related in: MedlinePlus