He Fu, Song Kangjian, Guan Ge, Huo Junyu, Xin Yang, Li Tianxiang, Liu Chao, Zhu Qingwei, Fan Ning, Guo Yuan, Wu Liqun
Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, People's Republic of China.
Department of Clinical Medicine, Qingdao University, Qingdao, 266071, Shandong, People's Republic of China.
Pharmgenomics Pers Med. 2021 Jun 21;14:723-736. doi: 10.2147/PGPM.S313848. eCollection 2021.
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).
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.
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; = 0.001). GR was identified as an independent risk factor for inferior DFS in HCCs (HR = 1.980, 95% CI = 1.246-3.147; = 0.004). However, there was no significant difference in SAR between GR-HCCs and NGR-HCCs receiving targeted therapy or immunotherapy.
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.
基因重排（GRs）已被报道与某些肿瘤的不良预后相关，但在肝细胞癌（HCC）中的关系仍研究较少。我们研究的目的是探讨伴有基因重排的HCC患者（GR-HCCs）的临床病理特征和预后。
这项回顾性研究纳入了297例行肝切除术且其肿瘤通过二代测序进行测序的HCC患者。组间分类变量采用卡方检验进行比较。采用Kaplan-Meier法和Cox回归分析变量对无病生存期（DFS）和复发后生存期（SAR）的影响。
我们在297例HCC中观察到4种重复性GR事件：BRD9/TERT、ARID2/基因间、CDKN2A/基因间和OBSCN截断。GR-HCCs常表现为肿瘤低分化、肿瘤坏死、微血管侵犯、甲胎蛋白升高和基因突变（TP53、NTRK3和BRD9）。GR-HCCs的1年、2年和3年累积DFS率分别为45.1%、31.9%、31.9%，显著低于GR阴性HCCs（NGR-HCCs）（分别为72.5%、57.9%和49.0%；P = 0.001）。GR被确定为HCC患者DFS较差的独立危险因素（HR = 1.980，95%CI = 1.246 - 3.147；P = 0.004）。然而，接受靶向治疗或免疫治疗的GR-HCCs和NGR-HCCs之间的SAR没有显著差异。
GR常与TP53突变相关，并显著影响HCC根治性切除术后的DFS。我们建议将GR-HCCs作为术后复发的高危组进行密切随访。
