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

Identifikátory výsledku

  • Kód výsledku v IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064173%3A_____%2F17%3AN0000216" target="_blank" >RIV/00064173:_____/17:N0000216 - isvavai.cz</a>

  • Nalezeny alternativní kódy

    RIV/00216208:11120/17:43911995 RIV/00216208:11130/17:10359513 RIV/61989592:15110/17:73583822 RIV/70883521:28150/17:63518096 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>

Alternativní jazyky

  • 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-rs2020903-rs4646034 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-rs2020903-rs4646034 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.

Klasifikace

  • Druh

    J<sub>imp</sub> - Článek v periodiku v databázi Web of Science

  • CEP obor

  • OECD FORD obor

    10608 - Biochemistry and molecular biology

Návaznosti výsledku

  • Projekt

  • Návaznosti

    V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Ostatní

  • Rok uplatnění

    2017

  • Kód důvěrnosti údajů

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

Údaje specifické pro druh výsledku

  • Název periodika

    Clinical Chemistry and Laboratory Medicine

  • ISSN

    1434-6621

  • e-ISSN

    1437-4331

  • 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