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

J 2021

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

BOUCHALOVÁ, Pavla, Jindřich BERÁNEK, Petr LAPČÍK, David POTĚŠIL, Ján PODHOREC et. al.

Basic information

Original name

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

Name in Czech

Transgelin přispívá ke slabé odpovědi metastatického renálního karcinomu na léčbu sunitinibem

Authors

BOUCHALOVÁ, Pavla (203 Czech Republic, belonging to the institution), Jindřich BERÁNEK (203 Czech Republic, belonging to the institution), Petr LAPČÍK (203 Czech Republic, belonging to the institution), David POTĚŠIL (203 Czech Republic, belonging to the institution), Ján PODHOREC (703 Slovakia, belonging to the institution), Alexandr POPRACH (203 Czech Republic, belonging to the institution) and Pavel BOUCHAL (203 Czech Republic, guarantor, belonging to the institution)

Edition

Biomedicines, Basel, MDPI, 2021, 2227-9059

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.757

RIV identification code

RIV/00216224:14310/21:00120144

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.3390/biomedicines9091145

UT WoS

000699070400001

Keywords in English

mccRCC; sunitinib; resistance; DIA-MS; transgelin

Abstract

V originále

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.

Links

NV19-08-00250, research and development project

Name: Proteotypová klasifikace renálního karcinomu ve vztahu k prognóze a terapeutické odpovědi

Investor: Ministry of Health of the CR

Citovat

BOUCHALOVÁ, Pavla, Jindřich BERÁNEK, Petr LAPČÍK, David POTĚŠIL, Ján PODHOREC, Alexandr POPRACH and Pavel BOUCHAL. Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment. Biomedicines. Basel: MDPI, 2021, vol. 9, No 9, p. 1145-1163. ISSN 2227-9059. Available from: https://dx.doi.org/10.3390/biomedicines9091145.

@article{1795618,
   author = {Bouchalová, Pavla and Beránek, Jindřich and Lapčík, Petr and Potěšil, David and Podhorec, Ján and Poprach, Alexandr and Bouchal, Pavel},
   article_location = {Basel},
   article_number = {9},
   doi = {http://dx.doi.org/10.3390/biomedicines9091145},
   keywords = {mccRCC; sunitinib; resistance; DIA-MS; transgelin},
   language = {eng},
   issn = {2227-9059},
   journal = {Biomedicines},
   title = {Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment},
   url = {https://www.mdpi.com/2227-9059/9/9/1145},
   volume = {9},
   year = {2021}
}

TY  - JOUR
ID  - 1795618
AU  - Bouchalová, Pavla - Beránek, Jindřich - Lapčík, Petr - Potěšil, David - Podhorec, Ján - Poprach, Alexandr - Bouchal, Pavel
PY  - 2021
TI  - Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment
JF  - Biomedicines
VL  - 9
IS  - 9
SP  - 1145
EP  - 1145
PB  - MDPI
SN  - 22279059
KW  - mccRCC
KW  - sunitinib
KW  - resistance
KW  - DIA-MS
KW  - transgelin
UR  - https://www.mdpi.com/2227-9059/9/9/1145
N2  - 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.
ER  -

BOUCHALOVÁ, Pavla, Jindřich BERÁNEK, Petr LAPČÍK, David POTĚŠIL, Ján PODHOREC, Alexandr POPRACH and Pavel BOUCHAL. Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment. \textit{Biomedicines}. Basel: MDPI, 2021, vol.~9, No~9, p.~1145-1163. ISSN~2227-9059. Available from: https://dx.doi.org/10.3390/biomedicines9091145.

Detailed Information on Publication Record