AUTHOR=Xin Zhaodan , Li Jin , Zhang Haili , Zhou Yi , Song Jiajia , Chen Piaopiao , Bai Ling , Chen Hao , Zhou Juan , Chen Jie , Ying Binwu 

TITLE=Cancer Genomic Alterations Can Be Potential Biomarkers Predicting Microvascular Invasion and Early Recurrence of Hepatocellular Carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.783109

DOI=10.3389/fonc.2022.783109

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>HCC patients without MVI had longer RFS than MVI ones (<italic>p</italic> &lt; 0.0001). The mutant incidence of genes like <italic>KEAP1, TP53</italic>, <italic>HIST1H3D</italic>, <italic>NFKBIA</italic>, <italic>PIK3CB</italic>, and <italic>WRN</italic> 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 (<italic>p</italic> &lt; 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, <italic>p</italic> = 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, <italic>p</italic> = 0.0062).</p></sec><sec><title>Conclusion</title><p>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.</p></sec>