Abstract
Abstract Introduction: Clear cell renal carcinoma is the most frequent form of renal malignancy, with an increasing incidence rate worldwide. In this study we used a multi-omic approach to differentiate normal and tumor tissues in clear cell Renal Cell Carcinoma (ccRCC). Methods: Using transcriptomic data of patients with malignant and adjacent normal tissue samples from gene chip and RNA-Seq cohorts, we identified the top genes over-expressed in ccRCC. We collected surgically resected ccRCC specimens to further investigate the transcriptomic results on the proteome level. The differential protein abundance was evaluated using targeted mass spectrometry (MS). Results: We assembled a database of more than 600 renal tissue samples from NCBI GEO and TCGA and used these to uncover the top genes with higher expression in ccRCC. For protein level analysis 162 malignant and normal kidney tissue samples have been acquired. The most consistently upregulated genes were IGFBP3, PLIN2, PLOD2, PFKP, VEGFA, and CCND1 (p<1E-05 for each gene). Mass spectrometry further validated the differential protein abundance of these genes (IGFBP3, p = 7.53E-18; PLIN2, p = 3.9E-39; PLOD2, p = 6.51E-36; PFKP, p = 1.01E-47; VEGFA, p = 1.40E-22; CCND1, p= 1.04E-24). We also identified proteins correlating with overall survival. Conclusions: We used transcriptomic and proteomic data to identify a minimal panel of proteins highly specific for clear cell renal carcinoma tissues. The introduced gene panel could be used as a promising tool in the clinical setting. Citation Format: Aron Bartha, Zsuzsanna Darula, Gyongyi Munkacsy, Eva Klement, David Fenyo, Peter Nyirady, Balazs Gyorffy. Insights of renal cell carcinoma from multiomic perspective [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB005.
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