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Molecular profile of 5-fluorouracil pathway genes in colorectal carcinoma
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SYSNO ASEP 0469539 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Molecular profile of 5-fluorouracil pathway genes in colorectal carcinoma Author(s) Kunická, T. (CZ)
Procházka, Pavel (UEM-P) RID
Krus, I. (CZ)
Bendová, Petra (UEM-P)
Protivová, M. (CZ)
Susová, S. (CZ)
Hlaváč, V. (CZ)
Liška, V. (CZ)
Novák, P. (CZ)
Schneiderová, M. (CZ)
Pitule, P. (CZ)
Bruha, J. (CZ)
Vyčítal, O. (CZ)
Vodička, Pavel (UEM-P) RID
Souček, P. (CZ)Source Title Bmc Cancer. - : BioMed Central
Roč. 16, oct. (2016), s. 795Number of pages 12 s. Language eng - English Country GB - United Kingdom Keywords colorectal carcinoma ; 5-fluorouracil ; methylation Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemistry and molecular biology R&D Projects NT14329 GA MZd - Ministry of Health (MZ) GAP304/12/1585 GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support UEM-P - RVO:68378041 UT WOS 000385590000006 EID SCOPUS 84991220464 DOI 10.1186/s12885-016-2826-8 Annotation Background: This study addresses involvement of major 5-fluorouracil (5-FU) pathway genes in the prognosis of colorectal carcinoma patients.
Methods: Testing set and two validation sets comprising paired tumor and adjacent mucosa tissue samples from 151 patients were used for transcript profiling of 15 5-FU pathway genes by quantitative real-time PCR and DNA methylation profiling by high resolution melting analysis. Intratumoral molecular profiles were correlated with clinical data of patients. Protein levels of two most relevant candidate markers were assessed by immunoblotting.
Results: Downregulation of DPYD and upregulation of PPAT, UMPS, RRM2, and SLC29A1 transcripts were found in tumors compared to adjacent mucosa in testing and validation sets of patients. Low RRM2 transcript level significantly associated with poor response to the first-line palliative 5-FU-based chemotherapy in the testing set and with poor disease-free interval of patients in the validation set irrespective of 5-FU treatment. UPP2 was strongly methylated while its transcript absent in both tumors and adjacent mucosa. DPYS methylation level was significantly higher in tumor tissues compared to adjacent mucosa samples. Low intratumoral level of UPB1 methylation was prognostic for poor disease-free interval of the patients (P = 0.0002). The rest of the studied 5-FU genes were not methylated in tumors or adjacent mucosa.
Conclusions: The observed overexpression of several 5-FU activating genes and DPYD downregulation deduce that chemotherapy naive colorectal tumors share favorable gene expression profile for 5-FU therapy. Low RRM2 transcript and UPB1 methylation levels present separate poor prognosis factors for colorectal carcinoma patients and should be further investigated.Workplace Institute of Experimental Medicine Contact Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2020 Electronic address https://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2826-8
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