TSC2 Mutations Were Associated with the Early Recurrence of Patients with HCC Underwent Hepatectomy
- PMID: 33623416
- PMCID: PMC7896791
- DOI: 10.2147/PGPM.S294307
TSC2 Mutations Were Associated with the Early Recurrence of Patients with HCC Underwent Hepatectomy
Abstract
Purpose: To explore the value of Tuberous sclerosis complex 2 (TSC2) 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 TSC2 mutations and recurrence rate within 1 year, RFS and OS after hepatectomy were analyzed.
Results: Our results showed that TSC2 mutation frequency in HCC was 12.6%. Compared to patients without TSC2 mutation, the proportion of microvascular invasion (MVI) and Edmondson grade III-IV was significantly higher in patients with a TSC2 mutation (p<0.05). The VAF of mutated TSC2 was higher in patients with maximum diameter of tumor >5cm or MVI than that of other patients (p<0.05). The frequency of TP53 mutation was significantly higher in patients with a TSC2 mutation than those without TSC2 mutation (p=0.003). Follow-up analysis showed that patients with a TSC2 mutation had significantly higher recurrence rate within 1 year (p=0.015) and poorer median recurrence-free survival (RFS) (p=0.010) than patients without TSC2 mutation. TSC2 mutations did not significantly affect overall survival of patients (p=0.480). The multivariate analysis results showed that the Barcelona Clinic Liver Cancer (BCLC) B-C stage, TSC2 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, p=0.000; HR=3.885, 95% CI: 1.295-11.653, p=0.015; HR=2.327, 95% CI: 1.018-5.323, p=0.045; respectively), and poorer RFS after hepatectomy (HR=3.070, 95% CI: 1.971-4.783, p=0.000; HR=1.861, 95% CI: 1.061-3.267, p=0.030; HR=1.715, 95% CI: 1.093-2.693, p=0.019; respectively).
Conclusion: TSC2 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.
Keywords: early recurrence; gene mutation; hepatocellular carcinoma; next-generation sequencing; tuberous sclerosis complex 2.
© 2021 Song et al.
Conflict of interest statement
All authors declare no conflicts of interest in this work.
Figures
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