The Phenomenon of Gene Rearrangement is Frequently Associated with TP53 Mutations and Poor Disease-Free Survival in Hepatocellular Carcinoma.

PURPOSE: Gene rearrangements (GRs) have been reported to be related to adverse prognosis in some tumours, but the relationship in hepatocellular carcinoma (HCC) remains less studied. The objective of our study was to explore the clinicopathological characteristics and prognosis of HCC patients (HCCs) with GRs (GR-HCCs). PATIENTS AND METHODS: This retrospective study included 297 HCCs who underwent hepatectomy and had their tumours sequenced by next-generation sequencing. Categorical variables between groups were compared by the chi-square test. The impact of variables on disease-free survival (DFS) and survival after relapse (SAR) was analysed by the Kaplan-Meier method and Cox regression. RESULTS: We observed four repetitive GR events in 297 HCCs: BRD9/TERT, ARID2/intergenic, CDKN2A/intergenic and OBSCN truncation. GR-HCCs frequently presented with low tumour differentiation, tumour necrosis, microvascular invasion, elevated AFP and gene mutations (TP53, NTRK3 and BRD9). The 1-, 2-, and 3-year cumulative DFS rates in GR-HCCs were 45.1%, 31.9%, 31.9%, respectively, which were significantly lower than those of GR-negative HCCs (NGR-HCCs) (72.5%, 57.9%, and 49.0%, respectively; P = 0.001). GR was identified as an independent risk factor for inferior DFS in HCCs (HR = 1.980, 95% CI = 1.246-3.147; P = 0.004). However, there was no significant difference in SAR between GR-HCCs and NGR-HCCs receiving targeted therapy or immunotherapy. CONCLUSION: GR is frequently associated with TP53 mutations and significantly affects DFS following radical resection for HCC. We recommend that GR-HCCs should be closely followed up as a high-risk group for postoperative recurrence.

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 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.

Severe Fatigue is an Important Factor in the Prognosis of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib.

OBJECTIVE: To investigate the effects of fatigue on the survival of patients with advanced hepatocellular carcinoma treated with sorafenib. PATIENTS AND METHODS: A retrospective analysis of 182 cases of patients with advanced hepatocellular carcinoma treated with sorafenib in our hospital from October 1, 2008, to October 31, 2017, showed clinical and pathological data and follow-up results. The clinical and pathological data as well as follow-up results of 182 patients with advanced hepatocellular carcinoma treated with sorafenib in our hospital from October 1, 2008, to October 31, 2018, were retrospectively analyzed. All patients were treated for at least 3 months. Patients were divided into three groups: fatigue grade I (n=74), fatigue grade II (n=62), and fatigue grade III (n=46), according to National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) version 5.0. Survival analysis between groups was performed by the Kaplan-Meier method (Log rank test), continuous variables were analyzed by t-test, and categorical variables were analyzed by chi-square test. RESULTS: The overall survival (OS) of patients who were relieved of fatigue was 33.0±9.3 months, whereas the OS of patients who were not relieved of fatigue was 15.0±1.8 months (P<0.000). Furthermore, the time to progress (TTP) of patients who were relieved of fatigue by resting was 20.3 ± 10.9 months compared to a TTP of 7.7 ± 1.0 months in patients who were not relieved of fatigue (P<0.000). CONCLUSION: Patients, especially the elderly and infirm, were more susceptible to toxicity.