Thymidine phosphorylase mRNA level predicts survival of patients with advanced oropharyngeal cancer.

Abstract

CONCLUSION:

The present study suggested that a high level of thymidine phosphorylase (TP) gene expression is significantly associated with favorable prognosis of patients treated with 5-fluorouracil (5-FU)-based chemotherapy. Further studies consisting of large series should be performed to confirm our present results.

BACKGROUND:

Expression levels of the thymidylate synthase (TS) and 5-FU metabolic enzymes including dihydropyrimidine dehydrogenase (DPD), TP, and orotate phosphoribosyl transferase (OPRT), are reported to be associated with sensitivity to 5-FU-based chemotherapy in several cancers.

PATIENTS AND METHODS:

Intratumoral mRNA expression levels of TS, DPD, TP, and OPRT in pretreatment biopsy specimens were quantified in 27 patients with advanced oropharyngeal squamous cell carcinomas. Association of these expression levels with response to platinum and 5-FU-based chemotherapy and survival were analyzed statistically.

RESULTS:

By Spearman's correlation analysis, significant correlation was observed between TS and TP (gamma=0.51, p=0.018). While no correlation was observed between the tumor regression and expression of any of the genes investigated, significant association was observed between prognosis and mRNA expression levels of TS and TP. Multivariate Cox regression analysis revealed that TP mRNA expression level is a significant factor predicting prognosis (hazard ratio (HR) = - 0.204, p=0.043).

• Authors: Takahiro Ijuin, Ken-ichi Nibu, Kiyoshi Doi, Hiroyuki Inoue, Miki Saitoh, Naoki Ohtsuki, Kunihiko Makino, Mutsuo Amatsu
• Journal: Acta oto-laryngologica (Acta Otolaryngol) Vol. 127 Issue 3 Pg. 305-11 (Mar 2007) ISSN: 0001-6489 [Print] England
• PMID: 17364369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• RNA, Messenger
• Dihydrouracil Dehydrogenase (NADP)
• Thymidylate Synthase
• Orotate Phosphoribosyltransferase
• Thymidine Phosphorylase
• Fluorouracil

Topics

• Adult
• Aged
• Antimetabolites, Antineoplastic (therapeutic use)
• Carcinoma, Squamous Cell (drug therapy, genetics, mortality)
• Dihydrouracil Dehydrogenase (NADP) (genetics)
• Female
• Fluorouracil (therapeutic use)
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Middle Aged
• Multivariate Analysis
• Oropharyngeal Neoplasms (drug therapy, genetics, mortality)
• Orotate Phosphoribosyltransferase (genetics)
• Polymerase Chain Reaction
• Prognosis
• RNA, Messenger (genetics)
• Statistics as Topic
• Thymidine Phosphorylase (genetics)
• Thymidylate Synthase (genetics)