Proteotype classification of renal cell carcinoma for prognosis and therapy response
| Autoři | |
|---|---|
| Rok publikování | 2023 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Renal cell carcinoma (RCC) has one of the highest incidences in the Czech Republic worldwide. However, reliable molecular markers related to critical clinical issues are still missing. To quantify proteins associated with pro-tumorigenic and pro-metastatic mechanisms in RCC, the RCC-specific spectral library of targeted proteomics assays was first generated, containing 7960 protein groups (FDR = 1%). Second, we analysed a set of localised RCC tissues (n=84) using data-independent acquisition mass spectrometry (DIA-MS), of which half relapsed in five years after diagnosis. We identified one key protein with the potential to predict relapse. CRISPR/Cas9 knockdown confirmed the role of this protein in cell migration and in the 3D spheroid assay in 786-0 cells, supporting its role in the metastatic potential of RCC cells. An independent migration/invasiveness method, transwell assay, is currently in progress to further verify the results. Third, we analysed a set of metastatic RCC tissues (training set n=53, validation set n=22) and adjacent non-cancerous tissues (n=17), of which a part of the tumours responded to the tyrosine kinase inhibitor (TKI) treatment, and a part did not. We identified one key protein associated with a poor response to TKI. CRISPR/Cas9 knockdown followed by cell migration assay, transwell assay and 3D spheroid assay confirmed its role in the metastatic potential of 786-0 cells. In summary, we successfully identified new potential prognostic and alternative therapeutic targets for localized and metastatic RCC using next-generation proteomics, and their functional validation is now in progress. |
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