Dihydropyrimidine dehydrogenase mRNA expression in peripheral blood of rectal cancer patients is significantly associated with residual tumor and distant metastases following resection.
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.
Hoffmann
Andreas-Claudius
AC
Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
Brabender
Jan
J
Metzger
Ralf
R
Ling
Fredericke
F
Warnecke-Eberz
Ute
U
Lurje
Georg
G
Hoelscher
Arnulf H
AH
Schneider
Paul M
PM
Vallböhmer
Daniel
D
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
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D013942:Thymine Nucleotides; D042943:Dihydrouracil Dehydrogenase (NADP); C024157:thymidine 5'-triphosphate