DIA-MS identified transmembrane glycoprotein GPNMB as a
candidate predictive biomarker and potentially a therapeutic
target in metastatic renal cell carcinoma

a 2025

DIA-MS identified transmembrane glycoprotein GPNMB as a candidate predictive biomarker and potentially a therapeutic target in metastatic renal cell carcinoma

ŠIMONÍK, Jan; Pavla BOUCHALOVÁ; Petr LAPČÍK; David POTĚŠIL; Ján PODHOREC et al.

Základní údaje

Originální název

DIA-MS identified transmembrane glycoprotein GPNMB as a candidate predictive biomarker and potentially a therapeutic target in metastatic renal cell carcinoma

Autoři

Vydání

In book of abstracts of Conference of the European Proteomics Association 2025, Saint-Malo June 16-20, 2025, 2025

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Označené pro přenos do RIV

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

metastatic renal cell carcinoma, tyrosine kinase inhibitor, sunitinib, pazopanib, TKI resistance, DIA proteomics, GPNMB, migration, invasiveness

Příznaky

Mezinárodní význam

Změněno: 3. 2. 2026 14:12, doc. Mgr. Pavel Bouchal, Ph.D.

Anotace

V originále

Background: Metastatic renal cell carcinoma (mRCC) has a poor prognosis in general, and the patients are commonly treated with receptor tyrosine kinase inhibitors (TKIs). However, about half of mRCC patients do not benefit from TKI treatment. Methods: To identify non-responders, we conducted a retrospective study of 53 mRCC tumors treated with TKI using data-independent acquisition mass spectrometry. To explore the identified protein as a potential therapeutic target, we knocked out its expression with CRISPR/Cas9 and studied migration and invasion in the 786-0 RCC cell line. Results: A total of 6183 protein groups (FDR 0.01) were quantified in the proteomics dataset. Differential protein abundance analysis identified 12 proteins associated with poor treatment response, of which 5 were confirmed in a validation cohort (n=22). Transmembrane glycoprotein B (GPNMB) had the highest predictive value for treatment response and was associated with progression-free survival. A trend of increased GPNMB levels was observed using immunohistochemistry (n = 40). Comparisons between parental and GPNMB-/- cells indicated that GPNMB enhances the migration and invasion capacity of 786-0 cells. Conclusions: GPNMB is a potential predictive biomarker for poor treatment response to TKIs and a potential therapeutic target for mRCC, as its blockade could overcome TKI resistance.

Návaznosti

LM2023042, projekt VaV

Název: Česká infrastruktura pro integrativní strukturní biologii

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CIISB - Česká infrastruktura pro integrativní strukturní biologii

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

MUNI/A/1684/2024, interní kód MU

Název: Podpora biochemického výzkumu v roce 2025

Investor: Masarykova univerzita, Podpora biochemického výzkumu v roce 2025

NW25-03-00122, projekt VaV

Název: Integrace multi-omics a bioinformatických nástrojů pro stanovení rizika relapsu renálního karcinomu a personalizaci adjuvantní onkologické léčby

Investor: Ministerstvo zdravotnictví ČR, Integrace multi-omics a bioinformatických nástrojů pro stanovení rizika relapsu renálního karcinomu a personalizaci adjuvantní onkologické léčby, Podprogram 1 - standardní

Citovat

ŠIMONÍK, Jan; Pavla BOUCHALOVÁ; Petr LAPČÍK; David POTĚŠIL; Ján PODHOREC; Lucia JANÁČOVÁ; Alice HLOBILKOVÁ; Kateřina JURÁSKOVÁ; Alexandr POPRACH; Milan HORA; Ondřej FIALA a Pavel BOUCHAL. DIA-MS identified transmembrane glycoprotein GPNMB as a candidate predictive biomarker and potentially a therapeutic target in metastatic renal cell carcinoma. In In book of abstracts of Conference of the European Proteomics Association 2025, Saint-Malo June 16-20, 2025. 2025.

@proceedings{2543376,
   author = {Šimoník, Jan and Bouchalová, Pavla and Lapčík, Petr and Potěšil, David and Podhorec, Ján and Janáčová, Lucia and Hlobilková, Alice and Jurásková, Kateřina and Poprach, Alexandr and Hora, Milan and Fiala, Ondřej and Bouchal, Pavel},
   booktitle = {In book of abstracts of Conference of the European Proteomics Association 2025, Saint-Malo June 16-20, 2025},
   keywords = {metastatic renal cell carcinoma, tyrosine kinase inhibitor, sunitinib, pazopanib, TKI resistance, DIA proteomics, GPNMB, migration, invasiveness},
   language = {eng},
   title = {DIA-MS identified transmembrane glycoprotein GPNMB as a candidate predictive biomarker and potentially a therapeutic target in metastatic renal cell carcinoma},
   year = {2025}
}

TY  - CONF
ID  - 2543376
AU  - Šimoník, Jan - Bouchalová, Pavla - Lapčík, Petr - Potěšil, David - Podhorec, Ján - Janáčová, Lucia - Hlobilková, Alice - Jurásková, Kateřina - Poprach, Alexandr - Hora, Milan - Fiala, Ondřej - Bouchal, Pavel
PY  - 2025
TI  - DIA-MS identified transmembrane glycoprotein GPNMB as a candidate predictive biomarker and potentially a therapeutic target in metastatic renal cell carcinoma
KW  - metastatic renal cell carcinoma, tyrosine kinase inhibitor, sunitinib, pazopanib, TKI resistance, DIA proteomics, GPNMB, migration, invasiveness
N2  - Background: Metastatic renal cell carcinoma (mRCC) has a poor prognosis in general, and the patients are commonly treated with receptor tyrosine kinase inhibitors (TKIs). However, about half of mRCC patients do not benefit from TKI treatment. Methods: To identify non-responders, we conducted a retrospective study of 53 mRCC tumors treated with TKI using data-independent acquisition mass spectrometry. To explore the identified protein as a potential therapeutic target, we knocked out its expression with CRISPR/Cas9 and studied migration and invasion in the 786-0 RCC cell line. Results: A total of 6183 protein groups (FDR 0.01) were quantified in the proteomics dataset. Differential protein abundance analysis identified 12 proteins associated with poor treatment response, of which 5 were confirmed in a validation cohort (n=22). Transmembrane glycoprotein B (GPNMB) had the highest predictive value for treatment response and was associated with progression-free survival. A trend of increased GPNMB levels was observed using immunohistochemistry (n = 40). Comparisons between parental and GPNMB-/- cells indicated that GPNMB enhances the migration and invasion capacity of 786-0 cells. Conclusions: GPNMB is a potential predictive biomarker for poor treatment response to TKIs and a potential therapeutic target for mRCC, as its blockade could overcome TKI resistance.
ER  -

ŠIMONÍK, Jan; Pavla BOUCHALOVÁ; Petr LAPČÍK; David POTĚŠIL; Ján PODHOREC; Lucia JANÁČOVÁ; Alice HLOBILKOVÁ; Kateřina JURÁSKOVÁ; Alexandr POPRACH; Milan HORA; Ondřej FIALA a Pavel BOUCHAL. DIA-MS identified transmembrane glycoprotein GPNMB as a candidate predictive biomarker and potentially a therapeutic target in metastatic renal cell carcinoma. In \textit{In book of abstracts of Conference of the European Proteomics Association 2025, Saint-Malo June 16-20, 2025}. 2025.

Přehled o publikaci