Measurement of DPD and TS Transcripts Aimed to Predict Clinical Benefit from Fluoropyrimidines: Confirmation of the Trend in Russian Colorectal Cancer Series and Caution Regarding the Gene Referees
- 29 May 2007
- journal article
- Published by S. Karger AG in Oncology Research and Treatment
- Vol. 30 (6), 295-300
- https://doi.org/10.1159/000102046
Abstract
Measurement of intratumoral expression of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) may have some value in predicting the response to fluoropyrimidine-containing therapy. Patients and Methods: We attempted to validate this association in a series of Russian metastatic colorectal cancer cases. While replicating already published protocols, we unexpectedly found that the use of commonly utilized gene referees, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and beta-actin, may lead to artifacts due to pseudogene-driven amplification from the genomic DNA template. We have developed a real-time PCR protocol which amplifies short PCR fragments, thus allowing efficient analysis of archival formalin-fixed paraffin-embedded tumor samples, and relies on succinate dehydrogenase (SDHA) as a gene referee, therefore avoiding amplification from genomic DNA. Results: Low content of DPD transcripts was observed in 13/20 (65%) patients with disease control (tumor response or disease stabilization) as compared to only 3/9 (33%) subjects with progressive disease (p = 0.11). Despite the low number of patients, this association reached the level of statistical significance when similar analysis was done for TS expression (11/20 (55%) vs. 1/9 (11%); p = 0.03). Conclusions: Our data confirm that low DPD and TS expressors have higher chances of success of fluoropyrimidine-containing regimens.Keywords
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