Transcript expression and genetic variability analysis of caspases in breast carcinomas suggests CASP9 as the most interesting target

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F70883521%3A28150%2F17%3A63518096" target="_blank" >RIV/70883521:28150/17:63518096 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/17:43911995 RIV/00216208:11130/17:10359513 RIV/61989592:15110/17:73583822 RIV/00064203:_____/17:10359513 a 2 dalších

Výsledek na webu

<a href="http://dx.doi.org/10.1515/cclm-2016-0271" target="_blank" >http://dx.doi.org/10.1515/cclm-2016-0271</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1515/cclm-2016-0271" target="_blank" >10.1515/cclm-2016-0271</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Transcript expression and genetic variability analysis of caspases in breast carcinomas suggests CASP9 as the most interesting target

Popis výsledku v původním jazyce

Background: Apoptosis plays a critical role in cancer cell survival and tumor development. We provide a hypothesis- generating screen for further research by exploring the expression profile and genetic variability of caspases (2, 3, 7, 8, 9, and 10) in breast carcinoma patients. This study addressed isoform-specific caspase transcript expression and genetic variability in regulatory sequences of caspases 2 and 9. Methods: Gene expression profiling was performed by quantitative real-time PCR in tumor and paired non-malignant tissues of two independent groups of patients. Genetic variability was determined by high resolution melting, allelic discrimination, and sequencing analysis in tumor and peripheral blood lymphocyte DNA of the patients. Results: CASP3 A+ B and S isoforms were over-expressed in tumors of both patient groups. The CASP9 transcript was down-regulated in tumors of both groups of patients and significantly associated with expression of hormonal receptors and with the presence of rs4645978-rs2020903rs4646034 haplotype in the CASP9 gene. Patients with a low intratumoral CASP9A/B isoform expression ratio (predicted to shift equilibrium towards anti-apoptotic isoform) subsequently treated with adjuvant chemotherapy had a significantly shorter disease-free survival than those with the high ratio (p = 0.04). Inheritance of CC genotype of rs2020903 in CASP9 was associated with progesterone receptor expression in tumors (p = 0.003). Conclusions: Genetic variability in CASP9 and expression of its splicing variants present targets for further study.

Název v anglickém jazyce

Transcript expression and genetic variability analysis of caspases in breast carcinomas suggests CASP9 as the most interesting target

Popis výsledku anglicky

Background: Apoptosis plays a critical role in cancer cell survival and tumor development. We provide a hypothesis- generating screen for further research by exploring the expression profile and genetic variability of caspases (2, 3, 7, 8, 9, and 10) in breast carcinoma patients. This study addressed isoform-specific caspase transcript expression and genetic variability in regulatory sequences of caspases 2 and 9. Methods: Gene expression profiling was performed by quantitative real-time PCR in tumor and paired non-malignant tissues of two independent groups of patients. Genetic variability was determined by high resolution melting, allelic discrimination, and sequencing analysis in tumor and peripheral blood lymphocyte DNA of the patients. Results: CASP3 A+ B and S isoforms were over-expressed in tumors of both patient groups. The CASP9 transcript was down-regulated in tumors of both groups of patients and significantly associated with expression of hormonal receptors and with the presence of rs4645978-rs2020903rs4646034 haplotype in the CASP9 gene. Patients with a low intratumoral CASP9A/B isoform expression ratio (predicted to shift equilibrium towards anti-apoptotic isoform) subsequently treated with adjuvant chemotherapy had a significantly shorter disease-free survival than those with the high ratio (p = 0.04). Inheritance of CC genotype of rs2020903 in CASP9 was associated with progesterone receptor expression in tumors (p = 0.003). Conclusions: Genetic variability in CASP9 and expression of its splicing variants present targets for further study.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

<a href="/cs/project/NT14055" target="_blank" >NT14055: Studie genetických faktorů korelujících s prognózou karcinomu prsu</a><br>

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Clinical Chemistry and Laboratory Medicine

ISSN

1434-6621

e-ISSN

—

Svazek periodika

55

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

12

Strana od-do

111-122

Kód UT WoS článku

000388930700021

EID výsledku v databázi Scopus

2-s2.0-84998694303