title: Comparison of 5-fluorouracil-related gene expression levels between adenocarcinomas and squamous cell carcinomas of the lung.
abstract: BACKGROUND
  A recent meta-analysis study showed that post-operative adjuvant chemotherapy with UFT, an oral combination drug composed of tegafur [prodrug of 5-fluorouracil (5-FU)] and uracil [inhibitor of dihydropyrimidine dehydrogenase (DPD)] was associated with improved survival in patients with lung adenocarcinomas, but not in those with lung squamous cell carcinomas.
  
  
  METHODS
  We investigated the 5-FU-related gene expression levels of thymidylate synthase (TS), DPD, thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) in resected tumor specimens from 51 patients with adenocarcinomas and 47 with squamous cell carcinomas using quantitative reverse transcription-PCR, and compared those levels between the two histological types.
  
  
  RESULTS
  The relative gene expression values of TS, TP and OPRT were significantly lower in adenocarcinomas compared with squamous cell carcinomas, 1.60 +/- 0.86 versus 4.33 +/- 3.40 (P < 0.001), 0.84 +/- 0.52 versus 2.27 +/- 1.16 (P = 0.006) and 9.59 +/- 6.30 versus 16.94 +/- 12.04 (P < 0.001), respectively. The relative gene expression value of DPD was significantly greater in adenocarcinomas than those in squamous cell carcinomas, 2.33 +/- 1.22 versus 1.50 +/- 1.20 (P = 0.01). Lower expressions of TS and TP were observed more in adenocarcinomas (89.8%) than in squamous cell carcinomas (48.9%) (P < 0.001).
  
  
  CONCLUSIONS
  These data may explain that post-operative adjuvant chemotherapy with UFT was associated with improved survival in stage I patients with adenocarcinoma, but less with squamous cell carcinoma.
authors.affiliation: Department of Cardiothoracic Surgery, Dokkyo Medical University, Shimotsuga, Tochigi, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ishihama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Chida
authors.forename: Osamu
authors.initials: O
authors.lastname: Araki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Karube
authors.forename: Norio
authors.initials: N
authors.lastname: Seki
authors.forename: Motohiko
authors.initials: M
authors.lastname: Tamura
authors.forename: Hideo
authors.initials: H
authors.lastname: Umezu
authors.forename: Koichi
authors.initials: K
authors.lastname: Honma
authors.forename: Nobuhide
authors.initials: N
authors.lastname: Masawa
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Miyoshi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D009962:Orotate Phosphoribosyltransferase / Q000235:genetics; D011379:Prognosis; D013939:Thymidine Phosphorylase / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics
chemical_list: D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D013939:Thymidine Phosphorylase; D005472:Fluorouracil