Objective:To investigate the molecular characterization of plasma extrachromosomal circular DNA(eccDNAs)in patients with clear cell renal carcinoma(ccRCC)and to screen for plasma differential expression of eccDNAs in ccRCC patients.Methods:The Tn5-tagmentation and next-generation sequencing(NGS)approach were applied for plasma eccDNAs detection in ccRCC patients and healthy controls.The length distribution,gene annotation,junctional nucleotide motif pattern and expression patterns of plasma eccDNAs were analyzed between ccRCC patients and those of healthy controls.Results:In ccRCC patients and healthy controls 8 568 and 8 150 plasma eccDNAs,respectively.No statistical differences of length distribution,gene annotation and motif signatures were observed between the two groups.Sequencing results showed that there were 701 differentially expressed eccDNAs in the plasma of ccRCC patients,of which 298 were up-regulated and 403 were down-regulated,and 25 ccRCC specific plasma eccDNAs have been screened.Among these eccDNAs,15 sequences mapped to known gene coding regions,7 mapped to known miRNA regions,and 3 mapped to known lincRNA regions.TCGA data showed that the expressions of 11 mapped genes of eccDNAs were significantly associated with the survival of ccRCC patients.Conclusion:This study demonstrated for the first time the presence of eccDNAs in the plasma of ccRCC patients with significantly altered expression profiles,suggesting that plasma eccDNAs is expected to be a new molecular marker for ccRCC.