Truncated isoform Vav3.1 is highly expressed in ovarian cancer stem cells and clinically relevant in predicting prognosis and platinum-response

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F18%3A10375247" target="_blank" >RIV/00216208:11140/18:10375247 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1002/ijc.31186" target="_blank" >https://doi.org/10.1002/ijc.31186</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ijc.31186" target="_blank" >10.1002/ijc.31186</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Truncated isoform Vav3.1 is highly expressed in ovarian cancer stem cells and clinically relevant in predicting prognosis and platinum-response

Popis výsledku v původním jazyce

Vav3 is a key modulator of GTP-hydrolases of the Rho/Rac family, which are crucially involved in cell proliferation. Vav3 is alternatively spliced in full-length Vav3-alpha and N-terminal truncated Vav3.1 lacking its self-regulatory domains. The aim of our study was to estimate the clinical impact of Vav3 and all other Vav family members in ovarian cancer. Purification of a stem-cell like side-population (SP) from ovarian cancer cell lines was performed by flow cytometry/FACS. Differences in gene expression between SP and NSP were assessed by Gene Array analysis and confirmed by RT-PCR and immunoblot. In addition, Vav mRNA expression was determined in 150 epithelial ovarian cancers. Clinicopathological parameters, platinum-sensitivity and survival were analyzed and associated with Vav expression. SP fractions of ovarian cancer cell lines exhibited marked overexpression of Vav3.1 (p&lt;0.001). Vav1 and Vav2 did not prove to be of clinicopathologic relevance in ovarian cancer. High Vav3.1 expression correlated with higher FIGO stage and residual disease. Furthermore, Vav3.1 overexpression was associated with poor progression-free (HR = 2.820, p = 0.0001) and overall survival (HR = 2.842, p = 0.0001). Subgroup analyses revealed an impact of Vav3.1 on survival in Type-II but not in Type-I cancers. Notably, platinum-refractory cancers showed marked overexpression of Vav3.1 compared to other subsets of platinum-sensitivity (15.848 vs. 6.653, p = 0.0001). In conclusion, Vav3.1 is over-expressed in stem-cell like SP fractions and is clinically relevant in the pathophysiology of ovarian cancer. The N-terminal truncated Vav3.1 may be decisively involved in mechanisms causing genuine multi-drug resistance.

Název v anglickém jazyce

Truncated isoform Vav3.1 is highly expressed in ovarian cancer stem cells and clinically relevant in predicting prognosis and platinum-response

Popis výsledku anglicky

Vav3 is a key modulator of GTP-hydrolases of the Rho/Rac family, which are crucially involved in cell proliferation. Vav3 is alternatively spliced in full-length Vav3-alpha and N-terminal truncated Vav3.1 lacking its self-regulatory domains. The aim of our study was to estimate the clinical impact of Vav3 and all other Vav family members in ovarian cancer. Purification of a stem-cell like side-population (SP) from ovarian cancer cell lines was performed by flow cytometry/FACS. Differences in gene expression between SP and NSP were assessed by Gene Array analysis and confirmed by RT-PCR and immunoblot. In addition, Vav mRNA expression was determined in 150 epithelial ovarian cancers. Clinicopathological parameters, platinum-sensitivity and survival were analyzed and associated with Vav expression. SP fractions of ovarian cancer cell lines exhibited marked overexpression of Vav3.1 (p&lt;0.001). Vav1 and Vav2 did not prove to be of clinicopathologic relevance in ovarian cancer. High Vav3.1 expression correlated with higher FIGO stage and residual disease. Furthermore, Vav3.1 overexpression was associated with poor progression-free (HR = 2.820, p = 0.0001) and overall survival (HR = 2.842, p = 0.0001). Subgroup analyses revealed an impact of Vav3.1 on survival in Type-II but not in Type-I cancers. Notably, platinum-refractory cancers showed marked overexpression of Vav3.1 compared to other subsets of platinum-sensitivity (15.848 vs. 6.653, p = 0.0001). In conclusion, Vav3.1 is over-expressed in stem-cell like SP fractions and is clinically relevant in the pathophysiology of ovarian cancer. The N-terminal truncated Vav3.1 may be decisively involved in mechanisms causing genuine multi-drug resistance.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

International Journal of Cancer

ISSN

0020-7136

e-ISSN

—

Svazek periodika

142

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

12

Strana od-do

1640-1651

Kód UT WoS článku

000425184800016

EID výsledku v databázi Scopus

2-s2.0-85038018482