title: Dihydropyrimidine dehydrogenase mRNA expression in peripheral blood of rectal cancer patients is significantly associated with residual tumor and distant metastases following resection.
abstract: BACKGROUND
  DPD and TS expression have been shown to correlate with response of 5-FU based chemotherapy in colorectal cancer tissue. Little is known about mRNA expression levels of TS and DPD in peripheral blood. The goals of this study were to test the feasibility of DPD and TS detection in blood and their associations to TNM staging and complete surgical resection.
  
  
  METHODS
  Whole blood was drawn 1 day pre- and 10 days post-operatively from 23 patients with rectal cancer. Either adjuvant (n = 15) or neoadjuvant (n = 8) treatment was performed. Tumor cells were enriched from whole blood by density gradient centrifugation prior to extraction of total cellular RNA and subsequent direct quantitative reverse transcriptase-PCR assays.
  
  
  RESULTS
  DPD was detectable in 21/23 patients (91.3%) and TS in 14/23 (61.7%). Stepwise multiple linear regression models showed a significant association of DPD expression with distant metastases (P = 0.004) and residual tumor categories (P = 0.03).
  
  
  CONCLUSIONS
  Quantitative analysis of TS and DPD mRNA expression in peripheral blood of rectal cancer patients is technically feasible. DPD expression levels appear to be associated with residual tumor categories and might serve as a molecular marker for complete tumor resection. Larger studies seem to be warranted to scrutinize our hypothesis.
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
authors.forename: Andreas-Claudius
authors.initials: AC
authors.lastname: Hoffmann
authors.forename: Jan
authors.initials: J
authors.lastname: Brabender
authors.forename: Ralf
authors.initials: R
authors.lastname: Metzger
authors.forename: Fredericke
authors.initials: F
authors.lastname: Ling
authors.forename: Ute
authors.initials: U
authors.lastname: Warnecke-Eberz
authors.forename: Georg
authors.initials: G
authors.lastname: Lurje
authors.forename: Arnulf H
authors.initials: AH
authors.lastname: Hoelscher
authors.forename: Paul M
authors.initials: PM
authors.lastname: Schneider
authors.forename: Daniel
authors.initials: D
authors.lastname: Vallböhmer
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000556:secondary / Q000601:surgery*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D017024:Chemotherapy, Adjuvant; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism*; D005240:Feasibility Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000201:enzymology*; D010865:Pilot Projects; D011184:Postoperative Period; D012333:RNA, Messenger / Q000032:analysis; D012372:ROC Curve; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D015996:Survival Rate; D013942:Thymine Nucleotides / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D013942:Thymine Nucleotides; D042943:Dihydrouracil Dehydrogenase (NADP); C024157:thymidine 5'-triphosphate