Xin Zhaodan, Li Jin, Zhang Haili, Zhou Yi, Song Jiajia, Chen Piaopiao, Bai Ling, Chen Hao, Zhou Juan, Chen Jie, Ying Binwu
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
Med+ Molecular Diagnostics Institute of West China Hospital/West China School of Medicine, Chengdu, China.
Front Oncol. 2022 Jan 27;12:783109. doi: 10.3389/fonc.2022.783109. eCollection 2022.
High recurrence incidence and poor survival after hepatectomy are enormous threats to hepatocellular carcinoma (HCC) patients, which can be caused by microvascular invasion (MVI). However, it is difficult to predict preoperative MVI status. In this study, we focus on cancer genomic alterations to comprehensively explore potential MVI and early recurrence biomarkers and provide clues to the mechanisms of HCC invasion and metastasis.
Forty-one patients with initially suspected HCC who were undergoing hepatectomy were finally enrolled. High-throughput targeted sequencing was performed on genomic alterations in their preoperative plasma and surgical fresh tumor tissues utilizing the 1,021-gene panel.
HCC patients without MVI had longer RFS than MVI ones ( < 0.0001). The mutant incidence of genes like , , , , and was higher in both MVI and early-recurrence patients than their counterparts. Besides, the alteration rates of Rap1 and Ras signaling pathways were significantly higher in MVI patients than NMVI ones ( < 0.05), and a similar trend of differences was also found in early-recurrence/non-recurrence comparison. The maximal variant allele frequency (VAF) of circulating tumor DNA (ctDNA) was statistically higher in MVI patients than NMVI ones (0.038 vs. 0.012, = 0.0048). With the cutoff value of 0.018, ctDNA maximal VAF could potentially predict the presence of MVI with an AUC of 0.85 (95% CI 0.693-0.998, = 0.0062).
The integration of a panel containing specific mutated genes and ctDNA maximal VAF for predicting MVI and early recurrence of HCC may achieve better performance.
肝切除术后高复发率和低生存率对肝细胞癌（HCC）患者构成巨大威胁，这可能由微血管侵犯（MVI）引起。然而，术前MVI状态难以预测。在本研究中，我们聚焦于癌症基因组改变，以全面探索潜在的MVI和早期复发生物标志物，并为HCC侵袭和转移机制提供线索。
最终纳入41例最初怀疑为HCC且接受肝切除术的患者。利用1021基因panel对其术前血浆和手术新鲜肿瘤组织中的基因组改变进行高通量靶向测序。
无MVI的HCC患者的无复发生存期（RFS）比有MVI的患者更长（<0.0001）。在MVI患者和早期复发患者中，如、、、和等基因的突变发生率均高于相应的对照组。此外，MVI患者中Rap1和Ras信号通路的改变率显著高于无MVI患者（<0.05），在早期复发/未复发比较中也发现了类似的差异趋势。MVI患者循环肿瘤DNA（ctDNA）的最大变异等位基因频率（VAF）在统计学上高于无MVI患者（0.038对0.012，=0.0048）。以0.018为临界值，ctDNA最大VAF有可能预测MVI的存在，AUC为0.85（95%CI 0.693-0.998，=0.0062）。
整合包含特定突变基因和ctDNA最大VAF的panel用于预测HCC的MVI和早期复发可能会有更好的表现。
