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中国癌症防治杂志

中国癌症防治杂志 ›› 2022, Vol. 14 ›› Issue (6): 630-636.doi: 10.3969/j.issn.1674-5671.2022.06.06

• 临床研究 • 上一篇    下一篇

基于血浆游离DNA片段组学特征的肝细胞癌预后分析

  

  1. 空军军医大学第一附属医院肝胆外科；空军军医大学基础医学院生理与病理生理学教研室
  • 出版日期:2022-12-25 发布日期:2022-12-30
  • 通讯作者: 安家泽 E?mail： anchen@fmmu.edu.cn
  • 基金资助:
    国家自然科学基金项目（82172919）；西京医院助推项目（XJZT21CZ02）；徐州市重点研发计划项目（KC21212；KC19172）

Prognostic analysis of hepatocellular carcinoma based on characteristics of plasma cell⁃free DNA fragmentomics

  • Online:2022-12-25 Published:2022-12-30

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摘要： 目的 探讨血浆游离DNA（cell⁃free DNA，cfDNA）片段组学特征在肝细胞癌（hepatocellular carcinoma，HCC）预后分析中的应用价值。方法 选取2016年6月至2016年9月空军军医大学第一附属医院肝胆外科收治的50例HCC患者为研究对象。采集HCC患者术前静脉血进行cfDNA提取、文库构建与测序，分析HCC患者cfDNA片段组学特征，包括片段大小分布和末端碱基基序。采用患者临床资料结合cfDNA片段组学数据进行Cox回归分析，筛选影响HCC患者预后的独立危险因素并构建列线图模型以预测HCC患者的总生存率。结果 cfDNA片段大小主要集中在150~200 bp，峰值位于167 bp处；且在100~200 bp之间出现间隔约10 bp的连续峰值波。比较总片段范围内的末端碱基基序显示，除A⁃end与G⁃end、T⁃end与C⁃end的平均占比差异无统计学意义（均P>0.05）外，其余比较差异均有统计学意义（均P<0.001），每个末端碱基基序在短片段和长片段中的平均占比比较，差异亦有统计学意义（均P<0.001）。肿瘤的分化程度、BCLC分期、片段大小得分是影响HCC患者预后的独立危险因素（均P<0.05）。基于上述3个因素构建列线图模型，其预测HCC患者1年和3年总生存率的受试者工作特征（receiver operating characteristic curve，ROC）曲线下面积分别为0.836和0.840。结论 cfDNA片段组学特征联合临床指标在HCC预后评估中具有较大的潜力。

关键词:  , 肝细胞癌；血浆游离DNA；片段组学；预后

Abstract: Objective To investigate  the value of plasma cell⁃free DNA (cfDNA) fragmentomics in the prognostic analysis of hepatocellular carcinoma (HCC). Methods A total of 50 HCC patients admitted to the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Fourth Military Medical University from June 2016 to September 2016 were selected as the subjects of study. Preoperative blood of HCC patients was collected for cfDNA extraction, library construction, and cfDNA sequencing. The cfDNA fragmentomic characteristics of HCC patients were analyzed, including fragment size distribution and terminal base motifs. The clinical data of patients combined with cfDNA fragmentomic data was performed by Cox regression analysis to screen independent factors affecting the prognosis of HCC patients, and a nomogram model was constructed to predict the overall survival rate of HCC patients. Results The cfDNA fragment sizes were mainly in the range of  150-200 bp, and the peak was at 167 bp; and continuous peak waves with an interval of about 10 bp appeared between 100-200 bp. Comparing the end motifs of total fragments, the differences were statistically significant (all P<0.001), except for the differences between the mean percentages of  A⁃end and G⁃end, and T⁃end and C⁃end (all P>0.05). Meanwhile, the differences between the mean proportion of each end motifs in the short fragments and the long fragments were also statistically significant (all P<0.001). The tumor differentiation, BCLC stage and fragment size score were independent factors affecting the prognosis of HCC patients(all P<0.05). Based on the above three factors to construct the nomogram model, the area under the receiver operating characteristic (ROC) curve for predicting  the 1⁃ and 3⁃year overall survival rate of HCC patients was 0.836 and 0.840, respectively. Conclusions  The combination of cfDNA fragmentomics and clinical indicators have great potential in the prognostic assessment of HCC. 

Key words: Hepatocellular carcinoma, Cell?free DNA, Fragmentomics, Prognosis

中图分类号: 

  • R735.7