Journal
CANCER SCIENCE
Volume 112, Issue 11, Pages 4772-4784Publisher
WILEY
DOI: 10.1111/cas.15128
Keywords
biomarkers; cell-free DNA; copy number variations; hepatocellular carcinoma; prognosis
Categories
Funding
- National Science and Technology major projects of China [2018ZX10302205-002]
- National Natural Science Foundation of China [81830070]
- Key Research and Development Program of Shaanxi Province, China [2018ZDXM-SF-061]
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This study found that CNVs in cfDNA were correlated with clinical outcomes in HCC patients undergoing radical treatments. Three genome-wide CNV indicators were associated with poorer OS and RFS, while high-frequency CNVs at chromosomal-arm level could predict HCC prognosis. A bin-level risk score was also constructed to enhance the prognostic ability of CNVs.
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.
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