DIA-MS identified transmembrane glycoprotein GPNMB as a candidate predictive biomarker and potentially a therapeutic target in metastatic renal cell carcinoma
| Autoři | |
|---|---|
| Rok publikování | 2025 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | 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. |
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