Renal Cell Carcinoma (RCC) encompasses a heterogeneous group of cancers derived from renal tubular epithelial cells and has a worldwide mortality. However, mortality rates have barely improved over the last 20 years. Novel biomarkers and biomarkers are thus urgently required for this cancer. The inventors have devised a strategy to produce mouse cancer cell lines of progressively enhanced aggressiveness and specialization. The mouse renal cancer cell line RENCA was serially passaged in vivo using multiple implantation strategies designed to replicate different aspects of primary tumour growth and metastasis. Transcriptomic and epigenomic data has been acquired for the derived cell lines and primary analyses have been performed. The inventors then selected plurality of genes with no reported role in RCC which were upregulated in their specialized cell lines, and checked their relevance in patient data and clinical samples. This approach contributes to identify 4 serum biomarkers, namely IL-34, SAA2, PONL1 and CFB that are suitable for predicting survival time in patients suffering from RCC. The inventors also validated that the 4 proteins are also biotargets for the treatment of RCC.