TSC2 Mutations Were Associated with the Early Recurrence of Patients with HCC Underwent Hepatectomy
Received 26 November 2020
Accepted for publication 26 January 2021
Published 16 February 2021 Volume 2021:14 Pages 269—278
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Martin Bluth
Kangjian Song, Fu He, Yang Xin, Ge Guan, Junyu Huo, Qingwei Zhu, Ning Fan, Yuan Guo, Yunjin Zang, Liqun Wu
Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China
Correspondence: Liqun Wu
Liver Disease Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Laoshan District, Qingdao, Shandong, 266003, People’s Republic of China
Tel +86 15315328331
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: hepatocellular carcinoma, tuberous sclerosis complex 2, next-generation sequencing, gene mutation, early recurrence
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