Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F21%3A00078866" target="_blank" >RIV/00209805:_____/21:00078866 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14310/21:00120144

Result on the web

<a href="https://pubmed.ncbi.nlm.nih.gov/34572331/" target="_blank" >https://pubmed.ncbi.nlm.nih.gov/34572331/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/biomedicines9091145" target="_blank" >10.3390/biomedicines9091145</a>

Result language

angličtina

Original language name

Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment

Original language description

Renal cell carcinoma (RCC) represents about 2-3% of all cancers with over 400,000 new cases per year. Sunitinib, a vascular endothelial growth factor tyrosine kinase receptor inhibitor, has been used mainly for first-line treatment of metastatic clear-cell RCC with good or intermediate prognosis. However, about one-third of metastatic RCC patients do not respond to sunitinib, leading to disease progression. Here, we aim to find and characterize proteins associated with poor sunitinib response in a pilot proteomics study. Sixteen RCC tumors from patients responding (8) vs. non-responding (8) to sunitinib 3 months after treatment initiation were analyzed using data-independent acquisition mass spectrometry, together with their adjacent non-cancerous tissues. Proteomics analysis quantified 1996 protein groups (FDR = 0.01) and revealed 27 proteins deregulated between tumors non-responding vs. responding to sunitinib, representing a pattern of deregulated proteins potentially contributing to sunitinib resistance. Gene set enrichment analysis showed an up-regulation of epithelial-to-mesenchymal transition with transgelin as one of the most significantly abundant proteins. Transgelin expression was silenced by CRISPR/Cas9 and RNA interference, and the cells with reduced transgelin level exhibited significantly slower proliferation. Our data indicate that transgelin is an essential protein supporting RCC cell proliferation, which could contribute to intrinsic sunitinib resistance.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

<a href="/en/project/NV19-08-00250" target="_blank" >NV19-08-00250: Proteotype classification of renal cell carcinoma for prognosis and therapy response</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

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

Name of the periodical

BIOMEDICINES

ISSN

2227-9059

e-ISSN

—

Volume of the periodical

9

Issue of the periodical within the volume

9

Country of publishing house

CH - SWITZERLAND

Number of pages

19

Pages from-to

1145

UT code for WoS article

000699070400001

EID of the result in the Scopus database

2-s2.0-85114774824