Proteotype classification of renal cell carcinoma for prognosis
and therapy response

a 2022

Proteotype classification of renal cell carcinoma for prognosis and therapy response

ŠIMONÍK, Jan, Richard ŠTEFANÍK, Pavla BOUCHALOVÁ, Petr LAPČÍK, David POTĚŠIL et. al.

Základní údaje

Originální název

Proteotype classification of renal cell carcinoma for prognosis and therapy response

Autoři

ŠIMONÍK, Jan, Richard ŠTEFANÍK, Pavla BOUCHALOVÁ, Petr LAPČÍK, David POTĚŠIL, Ján PODHOREC, Milan HORA, Alexandr POPRACH, Ondřej FIALA a Pavel BOUCHAL

Vydání

In Book of Abstracts of 16the Central- and Eastern European Proteomic Conference, Praha 29.9.-1.10.2022, FrO-16. 2022

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Organizační jednotka

Přírodovědecká fakulta

Změněno: 26. 11. 2022 00:09, doc. Mgr. Pavel Bouchal, Ph.D.

Anotace

V originále

Renal cell carcinoma (RCC) represents a serious oncological disease with one of the highest incidences in the Czech Republic across the world. Reliable molecular prognostic and predictive biomarkers for RCC are mostly unavailable, namely at protein level. To quantify proteins associated with pro-tumorigenic and pro-metastatic mechanisms in RCC, we first generated a comprehensive RCC-specific spectral library of targeted proteomic assays for 7960 protein groups (FDR=1%) [1]. Second, we have applied data independent acquisition mass spectrometry (DIA-MS) on QExactive HF-X LC-MS system to analyze a well-characterized set of initially localized RCC tumors (n=86) of which a half exhibited a relapse in <5 years after diagnosis. We have identified a single potential biomarker and two protein classifiers able to predict the relapse, for which we have developed selected reaction monitoring assay for further validation and routine quantification. CRISPR/Cas9 knockdown confirmed the role of the key protein in cell migration in 786-0 cells, supporting its role in metastatic potential of RCC. Third, we have analyzed a well-characterized set of metastatic RCC tumors (training set n=53, validation set n=22) and adjacent non-cancerous tissues (n=17) a part of which responded and a part did not respond to tyrosine kinase inhibitor (TKI) treatment. We have identified and validated a single protein biomarker and one classifier associated with a poor response to TKI but not with tumor grade and lymph node status. Functional assays using CRISPR/Cas9 knockdown confirmed its role in metastatic potential of 786-0 cells. In a summary, next generation proteomics based on DIA-MS is a powerful tool to classify RCC tissues, to identify prognostic biomarkers and alternative therapeutic targets. Supported by Ministry of Health of the Czech Republic, project No. NV19-08-00250, all rights reserved, and by The project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU. CIISB, Instruct-CZ Centre of Instruct-ERIC EU consortium, funded by MEYS CR infrastructure project LM2018127, is gratefully acknowledged for the financial support of the measurements at the CEITEC Proteomics Core Facility.

Návaznosti

LX22NPO5102, projekt VaV

Název: Národní ústav pro výzkum rakoviny (Akronym: NÚVR)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro výzkum rakoviny, 5.1 EXCELES

NV19-08-00250, projekt VaV

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

Investor: Ministerstvo zdravotnictví ČR, Proteotypová klasifikace renálního karcinomu ve vztahu k prognóze a terapeutické odpovědi

Citovat

ŠIMONÍK, Jan, Richard ŠTEFANÍK, Pavla BOUCHALOVÁ, Petr LAPČÍK, David POTĚŠIL, Ján PODHOREC, Milan HORA, Alexandr POPRACH, Ondřej FIALA a Pavel BOUCHAL. Proteotype classification of renal cell carcinoma for prognosis and therapy response. In In Book of Abstracts of 16the Central- and Eastern European Proteomic Conference, Praha 29.9.-1.10.2022, FrO-16. 2022.

@proceedings{2234238,
   author = {Šimoník, Jan and Štefaník, Richard and Bouchalová, Pavla and Lapčík, Petr and Potěšil, David and Podhorec, Ján and Hora, Milan and Poprach, Alexandr and Fiala, Ondřej and Bouchal, Pavel},
   booktitle = {In Book of Abstracts of 16the Central- and Eastern European Proteomic Conference, Praha 29.9.-1.10.2022, FrO-16.},
   language = {eng},
   title = {Proteotype classification of renal cell carcinoma for prognosis and therapy response},
   url = {https://www.czechms.org/cz/events/cmsc/abstract.php?code=4094307},
   year = {2022}
}

TY  - CONF
ID  - 2234238
AU  - Šimoník, Jan - Štefaník, Richard - Bouchalová, Pavla - Lapčík, Petr - Potěšil, David - Podhorec, Ján - Hora, Milan - Poprach, Alexandr - Fiala, Ondřej - Bouchal, Pavel
PY  - 2022
TI  - Proteotype classification of renal cell carcinoma for prognosis and therapy response
UR  - https://www.czechms.org/cz/events/cmsc/abstract.php?code=4094307
N2  - Renal cell carcinoma (RCC) represents a serious oncological disease with one of the highest incidences in the Czech Republic across the world. Reliable molecular prognostic and predictive biomarkers for RCC are mostly unavailable, namely at protein level. To quantify proteins associated with pro-tumorigenic and pro-metastatic mechanisms in RCC, we first generated a comprehensive RCC-specific spectral library of targeted proteomic assays for 7960 protein groups (FDR=1%) [1]. Second, we have applied data independent acquisition mass spectrometry (DIA-MS) on QExactive HF-X LC-MS system to analyze a well-characterized set of initially localized RCC tumors (n=86) of which a half exhibited a relapse in <5 years after diagnosis. We have identified a single potential biomarker and two protein classifiers able to predict the relapse, for which we have developed selected reaction monitoring assay for further validation and routine quantification. CRISPR/Cas9 knockdown confirmed the role of the key protein in cell migration in 786-0 cells, supporting its role in metastatic potential of RCC. Third, we have analyzed a well-characterized set of metastatic RCC tumors (training set n=53, validation set n=22) and adjacent non-cancerous tissues (n=17) a part of which responded and a part did not respond to tyrosine kinase inhibitor (TKI) treatment. We have identified and validated a single protein biomarker and one classifier associated with a poor response to TKI but not with tumor grade and lymph node status. Functional assays using CRISPR/Cas9 knockdown confirmed its role in metastatic potential of 786-0 cells. In a summary, next generation proteomics based on DIA-MS is a powerful tool to classify RCC tissues, to identify prognostic biomarkers and alternative therapeutic targets. Supported by Ministry of Health of the Czech Republic, project No. NV19-08-00250, all rights reserved, and by The project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU. CIISB, Instruct-CZ Centre of Instruct-ERIC EU consortium, funded by MEYS CR infrastructure project LM2018127, is gratefully acknowledged for the financial support of the measurements at the CEITEC Proteomics Core Facility.
ER  -

ŠIMONÍK, Jan, Richard ŠTEFANÍK, Pavla BOUCHALOVÁ, Petr LAPČÍK, David POTĚŠIL, Ján PODHOREC, Milan HORA, Alexandr POPRACH, Ondřej FIALA a Pavel BOUCHAL. Proteotype classification of renal cell carcinoma for prognosis and therapy response. In \textit{In Book of Abstracts of 16the Central- and Eastern European Proteomic Conference, Praha 29.9.-1.10.2022, FrO-16.}. 2022.

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