Mutations Were Associated with the Early Recurrence of Patients with HCC Underwent Hepatectomy.

PURPOSE

To explore the value of Tuberous sclerosis complex 2 () mutations in evaluating the early recurrence of hepatocellular carcinoma (HCC) patients underwent hepatectomy.

PATIENTS AND METHODS

A total of 183 HCC patients were enrolled. Next-generation sequencing was performed on tumor tissues to analyze genomic alterations, tumor mutational burden and variant allele fraction (VAF). The associations between mutations and recurrence rate within 1 year, RFS and OS after hepatectomy were analyzed.

RESULTS

Our results showed that mutation frequency in HCC was 12.6%. Compared to patients without mutation, the proportion of microvascular invasion (MVI) and Edmondson grade III-IV was significantly higher in patients with a mutation (p<0.05). The VAF of mutated was higher in patients with maximum diameter of tumor >5cm or MVI than that of other patients (p<0.05). The frequency of mutation was significantly higher in patients with a mutation than those without mutation (p=0.003). Follow-up analysis showed that patients with a mutation had significantly higher recurrence rate within 1 year (=0.015) and poorer median recurrence-free survival (RFS) (=0.010) than patients without mutation. TSC2 mutations did not significantly affect overall survival of patients (=0.480). The multivariate analysis results showed that the Barcelona Clinic Liver Cancer (BCLC) B-C stage, mutations and preoperative serum alpha-fetoprotein level ≥400μg/L were independently associated with recurrence within 1 year after hepatectomy (HR=8.628, 95% CI: 3.836-19.405, =0.000; HR=3.885, 95% CI: 1.295-11.653, =0.015; HR=2.327, 95% CI: 1.018-5.323, =0.045; respectively), and poorer RFS after hepatectomy (HR=3.070, 95% CI: 1.971-4.783, =0.000; HR=1.861, 95% CI: 1.061-3.267, =0.030; HR=1.715, 95% CI: 1.093-2.693, =0.019; respectively).

CONCLUSION

mutations were significantly associated with MVI in liver para-carcinoma tissue and Edmondson grade III-IV in patients with HCC and were independently associated with recurrence within 1 year and poorer RFS after hepatectomy. The TSC2 mutation may be a potential predictor for early recurrence in HCC patients underwent hepatectomy.