A multiomics disease progression signature of low-risk ccRCC

Background: Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Identification of ccRCC likely to progress, despite an apparent low risk at the time of surgery, represents a key clinical issue. Methods: From a cohort of adult ccRCC patients (n=443), we selected low-risk tumors progressing within a 5-years average follow-up (progressors: P, n=8) and non-progressing (NP) tumors (n=16). Transcriptome sequencing, miRNA sequencing and proteomics were performed on tissues obtained at surgery. Our work suggests that LXR, FXR and macrophage activation pathways could be critically involved in the inhibition of the progression of low-risk ccRCC. Furthermore, a 10-component classifier could support an early identification of apparently low-risk ccRCC patients. Next-generation sequencing of microRNA from formalin-fixed samples obtained at initial surgery from 8 low-risk patients with progressing tumours and 16 patients with similar Leibovich score, tumour stage and size, creatinine levels and surgical treatment, not progressing to recurrence with metastasis. Key results were confirmed with qPCR, immunohistochemistry and in external data. *** Raw data is to be made available through dbGaP (controlled access) due to patient privacy concerns**** Expression profiling by high throughput sequencing; part of mulitomics dataset; This is microRNAseq dataset which is linked to mRNAseq data from GSE171955 and proteomics mass-spec data posted on PRIDE (https://www.ebi.ac.uk/pride (ongoing submission process))