Kinjal K Gajjar1, Hemangini H Vora2, Toral P Kobawala1, Trupti I Trivedi3, Nandita R Ghosh1. 1. 1 Tumor Biology Lab 2, Cancer Biology Department, The Gujarat Cancer & Research Institute, NCH Compound, Asarwa, Ahmedabad, Gujarat- India. 2. 2 Immuno-haematology Lab 1, Cancer Biology Department, The Gujarat Cancer & Research Institute, NCH Compound, Asarwa, Ahmedabad, Gujarat- India. 3. 3 Clinical Carcinogenesis Lab 3, Cancer Biology Department, The Gujarat Cancer & Research Institute, NCH Compound, Asarwa, Ahmedabad, Gujarat- India.
Abstract
INTRODUCTION: 5-flourouracil (5-FU) is one of the standard chemotherapeutic drugs used today in the treatment of colorectal cancer patients. Disruption of 5-FU metabolic pathway may contribute to altered effectiveness towards 5-FU-based therapy. Hence, the study of 5-FU metabolizing enzymes might have the potential efficacy to predict survival and response to treatment in colorectal cancer patients. MATERIALS AND METHODS: Immunohistochemical localization of 5-FU metabolic enzymes (TS, MTHFR, DPYD, and TP) was evaluated in 143 untreated patients with colorectal cancer; their prognostic and predictive values were also evaluated. RESULTS: Immuno-positivity for TS, MTHFR, DPYD, and TP was observed in 77%, 75%, 88%, and 96% of colorectal cancer patients, respectively. Univariate survival analysis in total patients showed that low DPYD expression significantly predicted adverse overall survival ( P=0.042). Moreover, subgroup of colon cancer patients with low TS expression was associated with unfavorable prognosis. TP expression also emerged as a prognosticator in the subgroup of early and advanced stage patients. Additionally, when effect of co-expression of 5-FU metabolic enzymes was evaluated in total patients, low coexpression of all four proteins was predictive of poor overall survival than for individuals expressing high coexpression of these proteins ( P=0.045). In contrast, none of the 5-FU metabolic enzymes-either singly or on coexpression-emerged as a useful biomarker of potential therapeutic value when evaluated in the subgroup of patients treated with 5-FU alone or 5-FU plus oxaliplatin. CONCLUSION: The above findings suggest that coexpression of 5-FU metabolic enzymes possess significant prognostic value and could be useful biomarkers in colorectal cancer patients.
INTRODUCTION:5-flourouracil (5-FU) is one of the standard chemotherapeutic drugs used today in the treatment of colorectal cancerpatients. Disruption of 5-FU metabolic pathway may contribute to altered effectiveness towards 5-FU-based therapy. Hence, the study of 5-FU metabolizing enzymes might have the potential efficacy to predict survival and response to treatment in colorectal cancerpatients. MATERIALS AND METHODS: Immunohistochemical localization of 5-FU metabolic enzymes (TS, MTHFR, DPYD, and TP) was evaluated in 143 untreated patients with colorectal cancer; their prognostic and predictive values were also evaluated. RESULTS: Immuno-positivity for TS, MTHFR, DPYD, and TP was observed in 77%, 75%, 88%, and 96% of colorectal cancerpatients, respectively. Univariate survival analysis in total patients showed that low DPYD expression significantly predicted adverse overall survival ( P=0.042). Moreover, subgroup of colon cancerpatients with low TS expression was associated with unfavorable prognosis. TP expression also emerged as a prognosticator in the subgroup of early and advanced stage patients. Additionally, when effect of co-expression of 5-FU metabolic enzymes was evaluated in total patients, low coexpression of all four proteins was predictive of poor overall survival than for individuals expressing high coexpression of these proteins ( P=0.045). In contrast, none of the 5-FU metabolic enzymes-either singly or on coexpression-emerged as a useful biomarker of potential therapeutic value when evaluated in the subgroup of patients treated with 5-FU alone or 5-FU plus oxaliplatin. CONCLUSION: The above findings suggest that coexpression of 5-FU metabolic enzymes possess significant prognostic value and could be useful biomarkers in colorectal cancerpatients.