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

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 tissu...

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Autores principales: Song, Kangjian, He, Fu, Xin, Yang, Guan, Ge, Huo, Junyu, Zhu, Qingwei, Fan, Ning, Guo, Yuan, Zang, Yunjin, Wu, Liqun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896791/
https://www.ncbi.nlm.nih.gov/pubmed/33623416
http://dx.doi.org/10.2147/PGPM.S294307
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author Song, Kangjian
He, Fu
Xin, Yang
Guan, Ge
Huo, Junyu
Zhu, Qingwei
Fan, Ning
Guo, Yuan
Zang, Yunjin
Wu, Liqun
author_facet Song, Kangjian
He, Fu
Xin, Yang
Guan, Ge
Huo, Junyu
Zhu, Qingwei
Fan, Ning
Guo, Yuan
Zang, Yunjin
Wu, Liqun
author_sort Song, Kangjian
collection PubMed
description 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.
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spelling pubmed-78967912021-02-22 TSC2 Mutations Were Associated with the Early Recurrence of Patients with HCC Underwent Hepatectomy Song, Kangjian He, Fu Xin, Yang Guan, Ge Huo, Junyu Zhu, Qingwei Fan, Ning Guo, Yuan Zang, Yunjin Wu, Liqun Pharmgenomics Pers Med Original Research 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. Dove 2021-02-16 /pmc/articles/PMC7896791/ /pubmed/33623416 http://dx.doi.org/10.2147/PGPM.S294307 Text en © 2021 Song et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Song, Kangjian
He, Fu
Xin, Yang
Guan, Ge
Huo, Junyu
Zhu, Qingwei
Fan, Ning
Guo, Yuan
Zang, Yunjin
Wu, Liqun
TSC2 Mutations Were Associated with the Early Recurrence of Patients with HCC Underwent Hepatectomy
title TSC2 Mutations Were Associated with the Early Recurrence of Patients with HCC Underwent Hepatectomy
title_full TSC2 Mutations Were Associated with the Early Recurrence of Patients with HCC Underwent Hepatectomy
title_fullStr TSC2 Mutations Were Associated with the Early Recurrence of Patients with HCC Underwent Hepatectomy
title_full_unstemmed TSC2 Mutations Were Associated with the Early Recurrence of Patients with HCC Underwent Hepatectomy
title_short TSC2 Mutations Were Associated with the Early Recurrence of Patients with HCC Underwent Hepatectomy
title_sort tsc2 mutations were associated with the early recurrence of patients with hcc underwent hepatectomy
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896791/
https://www.ncbi.nlm.nih.gov/pubmed/33623416
http://dx.doi.org/10.2147/PGPM.S294307
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