Relation between serum levels of cell-free DNA and inflammation status in hepatitis C virus-related hepatocellular carcinoma.

Our study revealed that the level of circulating cell-free DNA (cfDNA) is increased in the serum of patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). To gain insight into the mechanism underlying this phenomenon, we examined the association between cfDNA levels and various clinicopathological factors in 96 patients with HCV-related HCC and 99 non-HCC patients with HCV. Using pooled DNA microarray data, we profiled the expression patterns of inflammatory cytokine genes in 14 primary tumors from the group of HCC patients. We found that there were positive associations between the cfDNA level, aspartate aminotransferase levels and the number of leukocytes and neutrophils in patients with HCV-related HCC but not in non-HCC patients with HCV. The serum cfDNA level was not associated with other clinicopathological factors in HCC or non-HCC patients. A cluster analysis based on the inflammatory cytokine gene data revealed that HCCs with a high serum cfDNA level had increased levels of several inflammatory cytokine genes, suggesting that the serum cfDNA level is associated with the inflammatory status in primary tumors in HCV-related HCC.