Molecular profile of 5-fluorouracil pathway genes in colorectal carcinoma

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F75010330%3A_____%2F16%3A00011447" target="_blank" >RIV/75010330:_____/16:00011447 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11140/16:10326838 RIV/00216208:11110/16:10326838 RIV/00216208:11120/16:43912270 RIV/00669806:_____/16:10326838 and 2 more

Result on the web

<a href="http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2826-8" target="_blank" >http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2826-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12885-016-2826-8" target="_blank" >10.1186/s12885-016-2826-8</a>

Result language

angličtina

Original language name

Molecular profile of 5-fluorouracil pathway genes in colorectal carcinoma

Original language description

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.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

BMC Cancer

ISSN

1471-2407

e-ISSN

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Volume of the periodical

16

Issue of the periodical within the volume

795

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

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UT code for WoS article

000385590000006

EID of the result in the Scopus database

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