Genomic profiling informs therapies and prognosis for patients with hepatocellular carcinoma in clinical practice

Area of Science:

• Oncology
• Genetics
• Genomics

Background:

• Hepatocellular carcinoma (HCC) genomic research has identified potential therapeutic targets.
• Clinical validation and translation of these targets into improved patient survival remain limited.
• Assessing the clinical utility and patient benefit of genetic analysis in HCC is crucial.

Purpose of the Study:

• To evaluate the clinical feasibility, utility, and patient benefit of genetic analysis in Chinese HCC patients.
• To identify actionable genetic alterations and their correlation with clinical outcomes and immune cell infiltration.

Main Methods:

• Whole exome sequencing of tumor and blood samples from 111 Chinese HCC patients.
• Utilized 508-gene and 688-gene panels for comprehensive genetic profiling.
• Correlated genetic mutations with targeted therapy information, immune cell infiltration, and patient survival.

Main Results:

• Approximately 95% of patients exhibited gene variations relevant to targeted treatment.
• 50% of patients possessed clinically actionable mutations providing significant therapeutic insights.
• TP53 mutations were associated with increased immune cell infiltration, while CTNNB1 and KMT2D mutations showed decreased infiltration.
• SPEN, EPPK1, and BRCA2 mutations correlated with reduced median overall survival.
• MUC16 mutations were not associated with decreased survival and were identified as an independent protective factor post-hepatectomy.

Conclusions:

• This study bridges genetic discoveries with clinical application in HCC.
• Identifies potential biomarkers for predicting prognosis and guiding targeted therapy or immunotherapy.
• Highlights the clinical relevance of genetic profiling for personalized HCC treatment strategies.