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王瑨, 柳俨哲, 陈况, 钱自亮, 胡明根. 血浆循环核酸应用于肝细胞癌诊断与预后评价的初步探索[J]. 解放军医学院学报, 2021, 42(1): 10-16. DOI: 10.3969/j.issn.2095-5227.2021.01.003
引用本文: 王瑨, 柳俨哲, 陈况, 钱自亮, 胡明根. 血浆循环核酸应用于肝细胞癌诊断与预后评价的初步探索[J]. 解放军医学院学报, 2021, 42(1): 10-16. DOI: 10.3969/j.issn.2095-5227.2021.01.003
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WANG Jin, LIU Yanzhe, CHEN Kuang, QIAN Ziliang, HU Minggen. cfDNA in diagnosis and prognosis prediction of hepatocellular carcinoma[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2021, 42(1): 10-16. DOI: 10.3969/j.issn.2095-5227.2021.01.003
Citation: WANG Jin, LIU Yanzhe, CHEN Kuang, QIAN Ziliang, HU Minggen. cfDNA in diagnosis and prognosis prediction of hepatocellular carcinoma[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2021, 42(1): 10-16. DOI: 10.3969/j.issn.2095-5227.2021.01.003
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血浆循环核酸应用于肝细胞癌诊断与预后评价的初步探索

cfDNA in diagnosis and prognosis prediction of hepatocellular carcinoma

    摘要
  • 摘要:
      背景  以肝细胞肝癌(hepatocellular carcinoma，HCC)为主的肝肿瘤在中国人死亡危险因素中排第5位，肝细胞肝癌的5年生存率仅为12.5%，对确诊肝癌的患者进行分级治疗显得尤为重要。目前仍然没有被广泛接受可以在术前对肝细胞肝癌患者的微血管浸润(microvascular invasion，MVI)进行精准预测的方法。
      目的  探讨血浆循环核酸(circulating free DNA，cfDNA)在术前预测肝细胞肝癌微血管浸润风险中的作用。
      方法  连续收集解放军总医院第一医学中心肝胆外科2019年3 - 10月61例肝肿瘤患者术前外周血标本，根据术后病理结果选取其中43例诊断为肝细胞肝癌和6例良性肿瘤的患者进行基因组测序，并进行了染色体不稳定分析，即超灵敏染色体非整倍体检测(ultrasensitive-chromosomal aneuploidy detector，UCAD)得到染色体不稳定性(chromosome instability，CIN)评分，该评分是对比患者cfDNA与人类正常基因组的测序结果，通过数学方法计算出患者循环核酸不稳定性的程度。分析CIN对于诊断HCC、预测MVI及术后复发的价值。
      结果  对患者的CIN评分进行log10转换后，HCC患者的CIN评分高于良性病变患者，差异有统计学意义(3.152±0.421 vs 2.282±0.099，P=0.032)。血浆CIN评分 ≥ 1 697.5预测MVI阳性的敏感度为76.9%，特异性为86.7%，优于甲胎蛋白以及现有的预测模型。所有患者中位随访时间5个月，14例血浆CIN评分 ≥ 1 697.5的HCC患者中有5例在半年内复发(35.7%)，而29例CIN评分较低(＜1 697.5)的患者仅有2例(5.71%)复发(P=0.019)。
      结论  cfDNA染色体不稳定性评分 ≥ 1 697.5可在术前预测肝癌患者发生MVI的风险，优于现有的预测指标，并且提示术后早期复发的风险。

     

    Abstract:
      Background  Liver cancer, mainly as hepatocellular carcinoma (HCC), ranks the fifth among the risk factors for death in Chinese, and the five-year survival rate of HCC is only 12.5%. Therefore, it is particularly important to carry out treatment according tumor stage. Currently, there is still no widely accepted method to accurately predict microvascular invasion in patients with HCC before surgery.
      Objective  To investigate the role of circulating free DNA (cfDNA) in predicting the risk of microvascular invasion (MVI) and prognosis of hepatocellular carcinoma (HCC).
      Methods  Preoperative peripheral blood samples were collected from 61 patients with liver tumors from March to October in 2019 in the Department of Hepatobiliary Surgery of the First Medical Center of Chinese PLA General Hospital. According to the postoperative pathologic results, 43 patients were diagnosed with hepatocellular carcinoma and 6 cases with benign tumors. These blood specimens were genome sequenced, then their chromosome instability was analyzed. UCAD (Ultrasensitive-Chromosomal Aneuploidy Detector) was applied to get chromosome instability (chromosome instability, CIN) score, which made a comparison between the cfDNA of the patient and the sequencing results of the normal human genome, and calculated the degree of circulating nucleic acid instability of the patients through mathematical methods.
      Results  After log conversion, the CIN score of HCC patients was significantly higher than that of the benign lesions (3.152 ± 0.421 vs 2.282 ± 0.099, P=0.032). The sensitivity and specificity of plasma CIN score ≥ 1697.5 to predict MVI positive result was 76.9% and 86.7%, respectively, which was better than AFP and the existing prediction model. Among the 43 HCC patients, tumor recurred within half a year in 5 (35.7%) patients with high CIN score (≥ 1 697.5), while only 2 (5.71%) in patients with low CIN score (＜1 697.5) (P=0.019).
      Conclusion  cfDNA chromosomal instability score ≥ 1 697.5 can predict the risk of MVI in patients with liver cancer before surgery and suggest the risk of early postoperative recurrence, which is better than the existing prediction indicator.

     

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