Potency of Thymidylate Synthase in Predicting Prognosis and Therapeutic Response in Colorectal Cancer Patients


Authors : Dr. Kinjal Gajjar; Dr. Toral Mandalia; Disha Jethva; Dr. Jayendra Patel; Dr. Nandita Ghosh; Dr. Hemangini Vora

Volume/Issue : Volume 8 - 2023, Issue 7 - July

Google Scholar : https://bit.ly/3TmGbDi

Scribd : https://tinyurl.com/2t927edj

DOI : https://doi.org/10.5281/zenodo.8228602

Abstract : Thymidylate synthase (TS), a critical enzyme in 5-Flourouracil (5-FU) metabolism, plays a significant role in predicting survival and therapeutic response in colorectal cancer (CRC) patients. Present study evaluated prognostic as well as predictive utility of TS VNTR polymorphism, TS mRNA expression and its protein level in CRC patients. Total 143 CRC patients were enrolled. TS VNTR polymorphism and TS mRNA expression were studied by PCR and semiquantitative RT-PCR, respectively.With regard to prognosis, a trend of reduced relapse-free survival (RFS) was noted with carriers of 3R allele (2R/3R+3R/3R) in rectal cancer subgroup (P=0.065). Further, high TS mRNA expression was associated with unfavorable RFS in total CRC patients (P=0.038), as well as in the subgroups of early stage (P=0.073), rectal cancer (P=0.059) and single drug 5-FU treated patients (P=0.029). On the other side, low TS protein expression showed poorer RFS (P=0.050) and overall survival (OS) (P=0.071) in colon cancer subgroup. It can be concluded that TS could be beneficial prognostic and predictive marker to identify patients with poor clinical outcome and thus might be useful to choose effective treatment modalities for CRC patients.

Keywords : TS, Colorectal Cancer, VNTR polymorphism, mRNA, Protein, 5-FU, Immunohistochemistry, Prognosis

Thymidylate synthase (TS), a critical enzyme in 5-Flourouracil (5-FU) metabolism, plays a significant role in predicting survival and therapeutic response in colorectal cancer (CRC) patients. Present study evaluated prognostic as well as predictive utility of TS VNTR polymorphism, TS mRNA expression and its protein level in CRC patients. Total 143 CRC patients were enrolled. TS VNTR polymorphism and TS mRNA expression were studied by PCR and semiquantitative RT-PCR, respectively.With regard to prognosis, a trend of reduced relapse-free survival (RFS) was noted with carriers of 3R allele (2R/3R+3R/3R) in rectal cancer subgroup (P=0.065). Further, high TS mRNA expression was associated with unfavorable RFS in total CRC patients (P=0.038), as well as in the subgroups of early stage (P=0.073), rectal cancer (P=0.059) and single drug 5-FU treated patients (P=0.029). On the other side, low TS protein expression showed poorer RFS (P=0.050) and overall survival (OS) (P=0.071) in colon cancer subgroup. It can be concluded that TS could be beneficial prognostic and predictive marker to identify patients with poor clinical outcome and thus might be useful to choose effective treatment modalities for CRC patients.

Keywords : TS, Colorectal Cancer, VNTR polymorphism, mRNA, Protein, 5-FU, Immunohistochemistry, Prognosis

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