Significance of expression of pyrimidine metabolizing genes in colon cancer

Abstract

Background and study aims: The reprogramming of metabolic pathways in tumour cells is a crucial step to meet the increased requirements for their own growth. This process occurs through alterations in gene expression, polymorphisms, and epigenetic dysregulation of a number of metabolic genes. Several metabolic enzymatic pathways such as pyrimidine-metabolizing enzymes have been implicated in tumorigenesis and tumor progression.

Patients and methods: We measured the relative expression levels of three pyrimidine-metabolizing genes-thymidylate synthase (TYMS), thymidine phosphorylase (TYMP), and dihydropyrimidine dehydrogenase (DPYD)-in tumor tissue and adjacent normal-appearing mucosa in 50 colon cancer (CC) patients using real-time reverse-transcription polymerase chain reaction. Gene expression was also studied in relation to demographic and pathological criteria.

Results: The gene expression levels of both TYMS and TYMP were significantly higher in tumor tissue than normal adjacent tissue. Further, they showed an agreeable level of diagnostic performance as a means to discriminate between normal and tumor tissue; TYMS had high specificity (94%) but moderate sensitivity (60%), while TYPM showed average sensitivity (70%) and specificity (76%). Although DPYD expression was lower in tumor tissue than paracancerous tissue, this level did not reach the statistical significance. TYMS expression was significantly higher in moderately and poorly differentiated tumors than in well-differentiated ones. There was no significant association between gene expression and the remaining clinicopathological criteria (e.g., age, sex, tumor location, and metastasis). We found a positive correlation between the gene expression levels of TYMS and DPYD.

Conclusion: TYMS and TYMP messenger RNA levels seem to be plausible indicators in the diagnosis of CC, although further studies are warranted for validation.

Keywords: Colon cancer; Dihydropyrimidine dehydrogenase; Gene expression; Real-time reverse-transcription polymerase chain reaction; Thymidine phosphorylase; Thymidylate synthase.