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.