Single nucleotide variants in KIF14 gene may have prognostic value in breast cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F75010330%3A_____%2F22%3A00014084" target="_blank" >RIV/75010330:_____/22:00014084 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064203:_____/22:10447715 RIV/70883521:28150/22:63553138 RIV/00216208:11120/22:43924020 RIV/00216208:11130/22:10447715 RIV/00216208:11140/22:10447715

Výsledek na webu

<a href="https://link.springer.com/article/10.1007/s40291-022-00616-z" target="_blank" >https://link.springer.com/article/10.1007/s40291-022-00616-z</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s40291-022-00616-z" target="_blank" >10.1007/s40291-022-00616-z</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Single nucleotide variants in KIF14 gene may have prognostic value in breast cancer

Popis výsledku v původním jazyce

Introduction Human kinesin 14 (KIF14) is one of the 70 prognostic marker genes (so-called Amsterdam profile) previously identified by the microarray of breast carcinomas, and its high transcript expression in tumor specimens indicates a poor prognosis for patients. We performed a pilot study to explore the prognostic and predictive meaning of KIF14 germline genetic variability in breast cancer patients. Methods KIF14 coding sequence, including 5 ' and 3 ' untranslated regions and overlaps to introns for identification of splicing sites, was analyzed using next-generation sequencing in the testing set of blood DNA samples from 105 breast cancer patients with clinical follow-up. After rigorous evaluation of major allele frequency, haplotype blocks, in silico predicted functional aspects, expression quantitative trait loci, and clinical associations, eight single nucleotide variants were subsequently validated in the evaluation set of 808 patients. Results Carriers of minor alleles G (rs17448931) or T (rs3806362) had significantly shorter overall survival than wild type homozygotes (p = 0.010 and p = 0.023, respectively) thus successfully replicating the results of the testing set. Both associations remained significant in the multivariate Cox regression analysis, including molecular subtype and stage as covariates (hazard ratio, HR = 1.7, 95% confidence interval (CI) = 1.1-2.8 for rs17448931 and HR = 1.9, CI 1.2-3.0 for rs3806362). Discussion In conclusion, our preliminary data suggest that minor alleles in rs17448931 and rs3806362 of KIF14 represent candidate biomarkers of poor prognosis of breast cancer patients. After pending validation in independent populations and eventual functional characterization, these candidates might become useful biomarkers in the clinics.

Název v anglickém jazyce

Single nucleotide variants in KIF14 gene may have prognostic value in breast cancer

Popis výsledku anglicky

Introduction Human kinesin 14 (KIF14) is one of the 70 prognostic marker genes (so-called Amsterdam profile) previously identified by the microarray of breast carcinomas, and its high transcript expression in tumor specimens indicates a poor prognosis for patients. We performed a pilot study to explore the prognostic and predictive meaning of KIF14 germline genetic variability in breast cancer patients. Methods KIF14 coding sequence, including 5 ' and 3 ' untranslated regions and overlaps to introns for identification of splicing sites, was analyzed using next-generation sequencing in the testing set of blood DNA samples from 105 breast cancer patients with clinical follow-up. After rigorous evaluation of major allele frequency, haplotype blocks, in silico predicted functional aspects, expression quantitative trait loci, and clinical associations, eight single nucleotide variants were subsequently validated in the evaluation set of 808 patients. Results Carriers of minor alleles G (rs17448931) or T (rs3806362) had significantly shorter overall survival than wild type homozygotes (p = 0.010 and p = 0.023, respectively) thus successfully replicating the results of the testing set. Both associations remained significant in the multivariate Cox regression analysis, including molecular subtype and stage as covariates (hazard ratio, HR = 1.7, 95% confidence interval (CI) = 1.1-2.8 for rs17448931 and HR = 1.9, CI 1.2-3.0 for rs3806362). Discussion In conclusion, our preliminary data suggest that minor alleles in rs17448931 and rs3806362 of KIF14 represent candidate biomarkers of poor prognosis of breast cancer patients. After pending validation in independent populations and eventual functional characterization, these candidates might become useful biomarkers in the clinics.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Molecular Diagnosis & Therapy

ISSN

1177-1062

e-ISSN

1179-2000

Svazek periodika

26

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

NZ - Nový Zéland

Počet stran výsledku

14

Strana od-do

665-678

Kód UT WoS článku

000865194200001

EID výsledku v databázi Scopus

2-s2.0-85139223403