Multiple-level copy number variations in cell-free DNA for prognostic prediction of HCC with radical treatments

Copy number variations (CNVs) in cell-free DNA (cfDNA) are emerging as noninvasive biomarkers for various cancers. However, multiple-level analysis of cfDNA CNVs for hepatocellular carcinoma (HCC) patients with radical treatments remains uninvestigated. Here, CNVs at genome-wide, chromosomal-arm, and bin levels were analyzed in cfDNA from 117 HCC patients receiving radical treatments. Then, the relationship between cfDNA CNVs and clinical outcomes was explored. Our results showed that a concordant profile of CNVs was observed between cfDNA and tumor tissue DNA. Three genome-wide CNV indicators including tumor fraction (TFx), prediction score (P-score), and stability score (S-score) were calculated and demonstrated to exhibit significant correlation with poorer overall survival (OS) and recurrence-free survival (RFS). Furthermore, the high-frequency cfDNA CNVs at chromosomal-arm level including the loss of 4q, 17p, and 19p and the gain of 8q and 1q clearly predicted HCC prognosis. Finally, a bin-level risk score was constructed to improve the ability of CNVs in predicting prognosis. Altogether, our study indicates that the multiple-level cfDNA CNVs are significantly associated with OS and RFS in HCC patients with radical treatments, suggesting that cfDNA CNVs detected by low-coverage whole-genome sequencing (WGS) may be used as potential prognostic biomarkers of HCC patients.