Abstract
Lack of efficient biomarkers and clinical translation of molecular typing impedes the implementation of targeted therapy for hepatocellular carcinoma (HCC). High-throughput sequencing techniques represented by next-generation sequencing (NGS) are tools for detecting targetable genes. The objective of this study is to explore the genetic alterations associated with clinicopathological features and the risk of recurrence/metastasis in HCC. NGS analysis was conducted on formalin-fixed paraffin-embedded tissues from 164 resected liver samples obtained from Chinese patients. Morphologic subtypes were reviewed based on hematoxylin-eosin and immunohistochemistry staining, Correlation to the acquired molecular features were analyzed with clinicopathological information. We also retrieved follow-up information of the 123 transplanted cases from 2017 to 2019 to screen recurrence/metastasis-associated factors by univariate analysis. Generally, the most frequently mutated genes include TP53 and CTNNB1 which showed a trend of mutually exclusive mutation. Copy-number variant with the highest frequency was detected in TAF1 and CCND1 in 11q13.3 loci. Correlation analysis showed that various genetic alterations were associated with morphologic subtypes and other pathologic features. While gene signatures of proliferation/nonproliferation class were correlated with differentiation, satellite foci and other invasive morphological features. Macrotrabecular-massive subtype, TSC2 (tuberous sclerosis complex 2) mutation, Ki-67 expression, and other six factors were found to be associated with recurrence/metastasis after liver transplantation. Genetic alterations detected by NGS show correlation with not only pathological and clinical features, but also with recurrence/metastasis after liver transplantation. Further gene-level molecular typing will be practical for targeted therapy and individual recurrence risk assessment in HCC patients.
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