Abstract 720P
Background
High incidence of recurrence is a major challenge for the survival of hepatocellular carcinoma (HCC) patients. Few evidences are available to elucidate mechanisms of early recurrence in HCC patients. Exploring the genomic relation and evolutionary patterns between primary and recurrent tumors is important to prevent postoperative recurrence and improve long-term survival of HCC patients.
Methods
A total of 30 HCC patients with matched primary and recurrent tumor tissues or blood samples were enrolled, who underwent surgery at The Affiliated Hospital of Qingdao University from July 2016 to August 2021. All samples were performed for targeted next-generation sequencing (NGS) of at least 118 cancer genes. We analyzed the genetic alterations in primary and recurrent tumors and their association with HCC short-term recurrence.
Results
A total of 67 samples were collected, including 34 primary and 33 recurrent samples. Somatic genomic alterations including SNV, Indel, CNV and rearrangement/fusion, exhibited comparable numbers between the two lesion types, and most driver gene mutations had similar frequencies. Notably, patients with CTNNB1 mutations in primary tumors had longer time to recurrence (TTR) than wild-type patients (mTTR: 26.2 vs 13.6 months, p=0.031). The inter-lesion mutational status analysis for each patient showed that 80% (24/30) patients had shared mutations in both primary and recurrent lesions. Patients with shared mutations ≤10% had longer TTR than those with >10% (mTTR: 19.7 vs 10.0 months, p=0.014). We set one year as a cut-off between the short-term recurrence (STR, TTR<12 months) and long-term recurrence (LTR, TTR>12 months). In primary lesions, mutations in DNA damage response (DDR) pathway were significantly higher in LTR group than that in STR group (52.2% vs 9.1%, p=0.024), while TERT mutations were higher in the STR group (54.5% vs 17.4%, p=0.045).
Conclusions
In this study, we demonstrated that the mutational spectrum was consistently between primary and recurrent HCCs. Newly diagnosed HCC patients with TERT mutations were more likely to relapse in a short term, whereas patients with CTNNB1 or DDR pathway mutations would have a better prognosis.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Jingyu Cao.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.