Multiple-level copy number variations in cell-free DNA for prognostic prediction of HCC with radical treatments.
Multiple-level copy number variations in cell-free DNA for prognostic prediction of HCC with radical treatments.
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DOI：
10.1111/cas.15128
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发表时间：
2021-11
期刊：
影响因子：
5.7
通讯作者：
Xing J
中科院分区：
文献类型：
--
作者：
Wang Y;Zhou K;Wang X;Liu Y;Guo D;Bian Z;Su L;Liu K;Gu X;Guo X;Wang L;Zhang H;Tao K;Xing J
无细胞DNA （cfDNA）的拷贝数变异（CNVs）正成为各种癌症的非侵入性生物标志物。然而，对接受根治治疗的肝细胞癌（HCC）患者cfDNA CNVs的多水平分析仍未得到研究。本研究分析了117例接受根治治疗的HCC患者cfDNA中全基因组、染色体臂和bin水平的CNVs。然后，探讨cfDNA CNVs与临床结局的关系。结果表明，cfDNA与肿瘤组织DNA具有一致性的CNVs谱。计算了三个全基因组CNV指标，包括肿瘤分数（TFx）、预测评分（P - score）和稳定性评分（S - score），并证明与较差的总生存期（OS）和无复发生存期（RFS）有显著相关性。此外，染色体臂水平的高频cfDNA CNVs，包括4q、17p和19p的缺失以及8q和1q的增加，清楚地预测了HCC的预后。最后，构建了一个bin水平的风险评分，以提高CNVs预测预后的能力。总之，我们的研究表明，在接受根治治疗的HCC患者中，多水平cfDNA CNVs与OS和RFS显著相关，这表明通过低覆盖率全基因组测序（WGS）检测到的cfDNA CNVs可能被用作HCC患者潜在的预后生物标志物。不同水平的循环游离DNA （cfDNA）拷贝数变异（CNV）指标除了临床病理因素和cfDNA浓度外，为肝癌根治患者提供了重要的预后信息。该方法有助于拓宽基于cfDNA CNV分析揭示临床有用生物标志物的适用策略。
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. The circulating free DNA (cfDNA) copy number variation (CNV) indicators at different levels provide important prognosis information for hepatocellular carcinoma (HCC) patients with radical treatments beyond clinicopathologic factors and cfDNA concentration. This approach is helpful for broadening the applicable strategy to reveal clinically useful biomarkers based on cfDNA CNV analysis.
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影响因子：
12.3
作者：
Siravegna G;Bardelli A
通讯作者：
Bardelli A
影响因子：
--
作者：
Liao W;Yang H;Xu H;Wang Y;Ge P;Ren J;Xu W;Lu X;Sang X;Zhong S;Zhang H;Mao Y
通讯作者：
Mao Y
人肝细胞癌的染色体改变与探索性CGH荟萃分析的病因学和组织学等级相关。
影响因子：
8.8
作者：
Moinzadeh, P;Breuhahn, K;Stützer, H;Schirmacher, P
通讯作者：
Schirmacher, P
影响因子：
16.6
作者：
Leal, Alessandro;van Grieken, Nicole C. T.;Velculescu, Victor E.
通讯作者：
Velculescu, Victor E.
影响因子：
7.5
作者：
Dong, Fangyuan;Yang, Qin;Bao, Zhijun
通讯作者：
Bao, Zhijun