Relative level of thymidylate synthase mRNA expression in primary tumors and normal tissues predicts survival of patients with oral tongue squamous cell carcinoma.
Thymidylate synthase (TS) is a major target of 5-fluorouracil (5-FU) and dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme in the degradation of 5-FU. There are no studies investigating the comparison of TS and DPD mRNA expressions in oral tongue SCC (OSCC) and nontumor tissues obtained from the same patients. In addition, increased interest has been focused on the biological roles of TS and DPD as the independent prognostic factors as well as responsive determinants for cancer patients with 5-FU based therapy. We determined the expression levels of TS and DPD in tumor (T) and nontumor squamous epithelial tissues (N) of OSCC using real-time reverse transcription-polymerase chain reaction and evaluated whether the T/N ratio would correlate with clinicopathological factors. The mRNA expressions of TS and DPD were significantly higher in tumor areas than in nontumor areas. No correlation was found between the T/N ratio of each mRNA expression and gender, clinical stage, T classification, N classification or differentiation. The T/N ratio of TS in patients that died of disease was significantly higher than in patients with free of disease, whereas there were no relationships between The T/N ratio of DPD and disease status. Clinical follow-up data showed shorter overall survival periods for cases with high T/N ratio of TS than for cases with low T/N ratio of TS with the statistically significant. Our study showed that TS but not DPD seems to have prognostic value in OSCC. These findings suggest that the assessment of TS activity may be useful both in the management and in the treatment of OSCC.
Yasumatsu
Ryuji
R
Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. yasuryuj@qent.med.kyushu-u.ac.jp
Nakashima
Torahiko
T
Wakasaki
Takahiro
T
Ayada
Toranoshin
T
Kadota
Hideki
H
Masuda
Muneyuki
M
Toh
Satoshi
S
Shiratsuchi
Hideki
H
Komune
Shizuo
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000378:metabolism*; D014062:Tongue Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality; D055815:Young Adult
D017931:DNA Primers; D012333:RNA, Messenger; D013940:Thymidylate Synthase
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