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Published on: July 22, 2020
Identification of driver genes and target drugs-related genes in liver cancer based on targeted next generation
Yunlong Cui1, Liwei Sun2, Hailong Wang3
1Department of Hepatobiliary Oncology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Abstract:
The purpose of this study was to identify gene mutations, high frequency mutations, and driver genes in liver cancer, and the marketed approved drugs of these genes, to provide evidence for targeted treatment of liver cancer since it is one of the most common cancers worldwide. 34 patients with liver cancer were included, and their blood samples were collected. The pathway enrichment analysis of the mutation gene was carried out through the KEGG database, and the genes with marketed approved drugs were screened according to the Pharmalaxy database. A total of 6,612 mutations in 1,241 genes were identified in 34 patients, in which 22 genes mutated in at least 40% of the samples and were thought to be high frequency mutation genes. All the mutations were analyzed using the MutSigCV software, and 30 genes with q<0.1 and p<0.05 were selected out as driver genes. Among them, LRP1B, MYC, NF1, and KEAP1 were coincident with high frequency mutation genes, which were considered key driver genes. Afterward, 181 genes with p<0.05 in MutSigCV software were analyzed for pathway enrichment. These genes were mainly enriched in four pathways, including MAPK mTOR, p53/cell cycle, and JAK-STAT pathways. Finally, there were 15 genes in four pathways that had marketed approved target drugs. To conclude, LRP1B, MYC, NF1, and KEAP1 were the candidate key driver genes for liver cancer, which might provide new insights for targeted therapy of liver cancer.
Insights
This study identified key driver genes, including LRP1B, MYC, NF1, and KEAP1, in liver cancer. These findings offer potential targets for developing new liver cancer therapies.
Area of Science:
- Genomics
- Oncology
- Pharmacology
Background:
- Liver cancer is a prevalent global malignancy.
- Identifying genetic drivers is crucial for effective targeted therapies.
Purpose of the Study:
- To identify gene mutations, high-frequency mutations, and driver genes in liver cancer.
- To find marketed drugs targeting these identified genes for potential liver cancer treatment.
Main Methods:
- Genomic analysis of 34 liver cancer patients' blood samples.
- Pathway enrichment analysis using KEGG database.
- Drug target screening via Pharmalaxy database.
Main Results:
- Identified 6,612 mutations in 1,241 genes; 22 were high-frequency mutation genes.
- Selected 30 driver genes, with LRP1B, MYC, NF1, and KEAP1 highlighted as key drivers.
- Found 15 genes within MAPK, mTOR, p53/cell cycle, and JAK-STAT pathways with approved target drugs.
Conclusions:
- LRP1B, MYC, NF1, and KEAP1 are candidate key driver genes for liver cancer.
- These genes and associated pathways represent potential targets for novel liver cancer therapies.
