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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


Hoffmann, A C; Brabender, J; Metzger, R; Ling, F; Warnecke-Eberz, U; Lurje, G; Hoelscher, A H; Schneider, P M; Vallböhmer, D (2009). Dihydropyrimidine dehydrogenase mRNA expression in peripheral blood of rectal cancer patients is significantly associated with residual tumor and distant metastases following resection. Journal of Surgical Oncology, 99(5):296-301.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Visceral and Transplantation Surgery
04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2009
Deposited On:28 Jan 2010 12:13
Last Modified:05 Apr 2016 13:48
Publisher:Wiley-Blackwell
ISSN:0022-4790
Publisher DOI:https://doi.org/10.1002/jso.21233
PubMed ID:19180589

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