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. 2021 Feb 16:14:269-278.
doi: 10.2147/PGPM.S294307. eCollection 2021.

TSC2 Mutations Were Associated with the Early Recurrence of Patients with HCC Underwent Hepatectomy

Kangjian Song  1 , Fu He  1 , Yang Xin  1 , Ge Guan  1 , Junyu Huo  1 , Qingwei Zhu  1 , Ning Fan  1 , Yuan Guo  1 , Yunjin Zang  1 , Liqun Wu  1
Affiliations

TSC2 Mutations Were Associated with the Early Recurrence of Patients with HCC Underwent Hepatectomy

Kangjian Song et al. Pharmgenomics Pers Med. .

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.

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Conflict of interest statement

All authors declare no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Survival curves of RFS according to TSC2 mutational status evaluated by Kaplan–Meier method (n=183). There were 23 patients with a TSC2 mutation and 160 patients without TSC2 mutation. The median RFS of patients with a TSC2 mutation was 7.4 months, while the median RFS of patients without TSC2 mutation was 30.8 months. Patients with a TSC2 mutation had significantly poorer RFS than others (p=0.010).
Figure 2
Figure 2
Survival curves of OS according to TSC2 mutational status evaluated by Kaplan–Meier method (n=183). There were 23 patients with a TSC2 mutation and 160 patients without TSC2 mutation. TSC2 mutations did not significantly affect overall survival of patients (p=0.480).
Figure 3
Figure 3
Survival curves of RFS according to TSC2 mutational status evaluated by Kaplan–Meier method in patients with preoperative serum AFP level above 400μg/L (n=53). Median RFS between patients with a TSC2 mutation and patients without TSC2 mutation was 3.3 vs 10.7 months (p=0.061).
Figure 4
Figure 4
Survival curves of RFS according to TSC2 mutational status evaluated by Kaplan–Meier method in patients with BCLC stage B-C (n=55). Median RFS between patients with a TSC2 mutation and patients without TSC2 mutation was 2.5 vs 6.8 months (p=0.118).
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