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Dihydropyrimidine dehydrogenase mRNA expression in peripheral blood of rectal cancer patients is significantly associated with residual tumor and distant metastases following resection
Author(s) -
Hoffmann AndreasClaudius,
Brabender Jan,
Metzger Ralf,
Ling Fredericke,
WarneckeEberz Ute,
Lurje Georg,
Hoelscher Arnulf H.,
Schneider Paul M.,
Vallböhmer Daniel
Publication year - 2009
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.21233
Subject(s) - medicine , colorectal cancer , dihydropyrimidine dehydrogenase , stage (stratigraphy) , messenger rna , cancer , chemotherapy , oncology , rna extraction , adjuvant , pathology , gene expression , fluorouracil , gene , biology , thymidylate synthase , paleontology , biochemistry
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. J. Surg. Oncol. 2009;99:296–301. © 2009 Wiley‐Liss, Inc.