Transgelin contributes to a poor response of metastatic renal
cell carcinoma to sunitinib treatment

a 2020

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, Jindřich BERÁNEK, Petr LAPČÍK, David POTĚŠIL, Ján PODHOREC, Alexandr POPRACH and Pavel BOUCHAL

Edition

In Book of Abstract of: 19th Human Proteome Organization World Congress, HUPO Connect 2020, October 19-22, 2020, p. 45. 2020

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Sweden

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Organization unit

Faculty of Science

Keywords (in Czech)

renální karcinom, sunitinib, rezistence, DIA proteomika, transgelin

Keywords in English

renal carcinoma, sunitinib, resistance, DIA proteomics, transgelin

Abstract

V originále

Introduction. Renal cell carcinoma (RCC) represents about 2-3% of all cancers with over 400,000 new cases per year with an increasing incidence worldwide. Sunitinib, a vascular endothelial growth factor (VEGF) tyrosin kinase receptor inhibitor, has been used for first-line treatment of metastatic RCC (mRCC) with good or intermediate prognosis. About one third of mRCC patients, however, do not respond well to sunitinib. The aim of presented pilot study was to find proteins associated with poor sunitinib response. Methods. 8 vs. 8 RCC tumors from patients responding vs. non-responding to sunitinib in 3 months after treatment initiation, and their adjacent normal tissues, were analyzed using LC-MS proteomics in data independent acquisition (DIA) mode on Impact II LC-MS system (Bruker). The most promising proteins were functionally analyzed via CRISPR/Cas9 technology in 786-0 RCC cell line and using proliferation tests. Results. Proteomics analysis quantified 2012 protein groups (FDR<0.01) and revealed 42 proteins deregulated in primary tumors non-responding vs. responding to sunitinib. Gene set enrichment analysis showed enriched elastic fibres, vesicular transport and transport of small molecules pathways. Based on the above, transgelin, a well-known structural protein involved in actin remodeling, was selected for functional analysis. TAGLN gene was successfully disrupted by CRISPR/Cas9. The cells with reduced level of transgelin then exhibited significantly slower proliferation. Conclusion. DIA proteomics analysis revealed a pattern of de-regulated proteins possibly directly or indirectly contributing to sunitinib resistance. The data shows that transgelin supports survival of RCC cells and could contribute to their intrinsic sunitinib resistance.

Links

MUNI/A/1252/2019, interní kód MU

Name: Podpora biochemického výzkumu v roce 2020

Investor: Masaryk University, Category A

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. In In Book of Abstract of: 19th Human Proteome Organization World Congress, HUPO Connect 2020, October 19-22, 2020, p. 45. 2020.

@proceedings{1727645,
   author = {Bouchalová, Pavla and Beránek, Jindřich and Lapčík, Petr and Potěšil, David and Podhorec, Ján and Poprach, Alexandr and Bouchal, Pavel},
   booktitle = {In Book of Abstract of: 19th Human Proteome Organization World Congress, HUPO Connect 2020, October 19-22, 2020, p. 45.},
   keywords = {renal carcinoma, sunitinib, resistance, DIA proteomics, transgelin},
   language = {eng},
   title = {Transgelin contributes to a poor response of metastatic renal cell carcinoma to sunitinib treatment},
   url = {https://hupo2020.org/wp-content/uploads/2020/10/HUPO-Connect-2020-Abstract_Book_2020.10.15-NR.pdf},
   year = {2020}
}

TY  - CONF
ID  - 1727645
AU  - Bouchalová, Pavla - Beránek, Jindřich - Lapčík, Petr - Potěšil, David - Podhorec, Ján - Poprach, Alexandr - Bouchal, Pavel
PY  - 2020
TI  - Transgelin contributes to a poor response of metastatic renal cell carcinoma to sunitinib treatment
KW  - renal carcinoma, sunitinib, resistance, DIA proteomics, transgelin
UR  - https://hupo2020.org/wp-content/uploads/2020/10/HUPO-Connect-2020-Abstract_Book_2020.10.15-NR.pdf
N2  - Introduction. Renal cell carcinoma (RCC) represents about 2-3% of all cancers with over 400,000 new cases per year with an increasing incidence worldwide. Sunitinib, a vascular endothelial growth factor (VEGF) tyrosin kinase receptor inhibitor, has been used for first-line treatment of metastatic RCC (mRCC) with good or intermediate prognosis. About one third of mRCC patients, however, do not respond well to sunitinib. The aim of presented pilot study was to find proteins associated with poor sunitinib response. Methods. 8 vs. 8 RCC tumors from patients responding vs. non-responding to sunitinib in 3 months after treatment initiation, and their adjacent normal tissues, were analyzed using LC-MS proteomics in data independent acquisition (DIA) mode on Impact II LC-MS system (Bruker). The most promising proteins were functionally analyzed via CRISPR/Cas9 technology in 786-0 RCC cell line and using proliferation tests. Results. Proteomics analysis quantified 2012 protein groups (FDR<0.01) and revealed 42 proteins deregulated in primary tumors non-responding vs. responding to sunitinib. Gene set enrichment analysis showed enriched elastic fibres, vesicular transport and transport of small molecules pathways. Based on the above, transgelin, a well-known structural protein involved in actin remodeling, was selected for functional analysis. TAGLN gene was successfully disrupted by CRISPR/Cas9. The cells with reduced level of transgelin then exhibited significantly slower proliferation. Conclusion. DIA proteomics analysis revealed a pattern of de-regulated proteins possibly directly or indirectly contributing to sunitinib resistance. The data shows that transgelin supports survival of RCC cells and could contribute to their 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. In \textit{In Book of Abstract of: 19th Human Proteome Organization World Congress, HUPO Connect 2020, October 19-22, 2020, p. 45.}. 2020.

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