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Thymidylate synthase level and DNA-ploidy pattern as possible prognostic factors in human colorectal cancer: a
R Sanguedolce1, I Brumarescu, G Dardanoni
1Instituto di Farmacologia, Policlinico, Palermo, Italy.
Abstract:
5-Fluorouracil is the drug chosen for the treatment of patients with advanced colorectal carcinoma; its major site of action is thymidylate synthase (TS), resulting in pronounced and prolonged inhibition of DNA synthesis. The aim of this study was to evaluate the possibility of considering TS level in human colorectal carcinomas of previously untreated patients (pts) as a prognostic factor. Our data demonstrate that there is no association with age, sex, tumor site and tumor size; however, there is a relationship between TS levels and staging: in fact, the TS values are higher (P < 0.05) in Dukes-A tumors than in the others. A significant association was also found between the TS levels and survival parameters: in fact, pts with longer disease-free and overall survivals had a significantly increased TS level compared to pts with a poorer outcome (P < 0.05). Moreover, pts with DNA-aneuploid tumors had lower TS level (median = 0.044 pmol/mg protein) than diploid pts who had higher TS level (median = 0.093 pmol/mg protein); however the difference is not significant. Our result are based on preliminary data; however, they seem to support the hypothesis that a high TS level is a favourable prognostic factor in human colorectal carcinoma.
Insights
High thymidylate synthase (TS) levels in colorectal carcinoma patients may indicate a favorable prognosis. This suggests TS levels could be a valuable prognostic factor for predicting patient outcomes in colorectal cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- 5-Fluorouracil is a primary treatment for advanced colorectal carcinoma, targeting thymidylate synthase (TS).
- Understanding prognostic factors is crucial for optimizing colorectal cancer patient management.
Purpose of the Study:
- To investigate thymidylate synthase (TS) levels as a prognostic factor in previously untreated patients with human colorectal carcinoma.
- To evaluate the correlation between TS levels and clinicopathological features, including tumor staging and patient survival.
Main Methods:
- Analysis of TS levels in human colorectal carcinoma tissues from previously untreated patients.
- Correlation of TS levels with patient age, sex, tumor site, tumor size, and tumor stage (Dukes classification).
- Assessment of the association between TS levels and disease-free survival and overall survival rates.
Main Results:
- TS levels showed no association with age, sex, tumor site, or tumor size.
- Higher TS levels were observed in Dukes-A stage tumors compared to other stages (P < 0.05).
- Patients with longer disease-free and overall survival exhibited significantly higher TS levels (P < 0.05).
- A trend of lower TS levels in DNA-aneuploid tumors compared to diploid tumors was noted, though not statistically significant.
Conclusions:
- Preliminary data suggest that elevated thymidylate synthase (TS) levels may be a favorable prognostic indicator in human colorectal carcinoma.
- TS levels warrant further investigation as a potential biomarker for predicting treatment response and patient outcomes in colorectal cancer.